Diabetes

Mindi Rosen met Seuli Brill, MD, at just the right time. 

Ms. Rosen’s firstborn son was in the neointensive natal unit at The Ohio State University Wexner Medical Center in Columbus, and she didn’t have a pediatrician picked out yet for the baby. Nor did she have a primary care physician who could help her manage the gestational diabetes she developed during her pregnancy.

Dr. Brill, a clinical associate professor of internal medicine and pediatrics at Ohio State, suggested Ms. Rosen visit her at the new clinic she was piloting in Columbus. There, she provided pediatric care for newborns and primary care for mothers who had developed gestational diabetes.  

“I looked at my husband, my husband looked at me, and I said: ‘Why not?’ “ Ms. Rosen, 38, recalled of that 2019 meeting. “I’m so glad she walked in at that moment.”

The mother of two is still part of the rapidly growing program at the medical facility that provides care for more than 200 mothers and babies.

Launched in 2018, the clinic – called the Multi-Modal Maternal Infant Perinatal Outpatient Delivery System, or “Momi Pods,” started with a focus  on helping women with gestational diabetes, which occurs in up to 10% of pregnancies.

The program allows moms to book regular checkups for their baby, and then a follow-up appointment immediately after for themselves. Women are seen for the first 1,000 days (just under 3 years) after giving birth.

The idea was simple. Dr. Brill wanted to develop a more formalized program for the work she was already doing as a primary care physician and pediatrician. At the time, she was fielding referrals from specialists for young women who didn’t have a physician. She’d often develop a relationship with the patient over the years, go on to help oversee their care during pregnancy, then new mothers would select her as their newborn’s pediatrician.

“I would have a relationship with the mom when they did have the newborn, and then I would see the baby because I’m a pediatrician,” Dr. Brill said.

Dr. Brill was serving on the Ohio Gestational Diabetes Mellitus Collaborative, a state-backed program that aims to raise awareness about the condition and encourage more preventative care for patients. She presented her proposal to launch the program to the Ohio Department of Medicaid, which helped to fund the pilot.

The idea, she hoped, would improve postpartum follow-up care for mothers diagnosed with the condition. 

Follow-up care is especially important for women who develop gestational diabetes because the condition raises their lifetime risk of developing type 2 diabetes up to 10-fold. 

Yet most of those mothers don’t get the appropriate follow-up care during the crucial postpartum period, said Maya Subbalakshmi Venkataramani, MD, MPH, an assistant professor of medicine at Johns Hopkins University in Baltimore, who has researched parental care. 

“Things get very busy after you have a child. There’s just the general logistics of a mom having to take care of a newborn and thinking about themselves,” Dr. Venkataramani, a primary care clinician and pediatrician, said. “A lot of parents in general may not put a lot of emphasis on their own health.”

Seeking care may be especially difficult for low-income mothers who might not have consistent health care coverage, she added.

In fact, only half of women who developed gestational diabetes received primary follow-up care, according to a study published in JAMA Network Open. The study, which examined more than 280,000 insurance claims between 2015 and 2018, found only 36% of women with gestational diabetes received the recommended blood glucose testing in the first 12 weeks of the postpartum period.

In the Momi Pods program, Dr. Brill checked in on Ms. Rosen’s gestational diabetes regularly during pediatric office visits for her newborn’s care. Ms. Rosen said whenever she brought her baby in for a visit during the postpartum period, Dr. Brill measured her blood sugar. 

Dr. Brill and her team also asked how Ms. Rosen was doing physically and mentally during each visit. The screenings helped to catch a bout of postpartum depression Ms. Rosen experienced after the birth of her first son.

“I thought it was great, because honestly as a new mom I wouldn’t have followed up with myself so much,” Ms. Rosen said. “Every time you went into the doctor appointments, they’d ask you how you are doing. As a new mom, it’s so much easier to do it at the same time.”

Those who participate in the program are also more likely to complete postpartum visits with their ob.gyn. (95% vs. 58%, respectively; P < .001) than those who don’t participate, according to research Dr. Brill and colleagues published.

Dr. Brill began expanding the program’s reach nearly 2 years after its launch, targeting the services for women who are at risk for poor postpartum outcomes, including those with a history of depression, preterm labor, diabetes and congenital heart disease. Ob.gyns. in Ohio State’s network can refer their patients to the program, which now has 43 doctors trained to provide primary and pediatric care through Momi Pods. Soon-to-be moms can be referred to the program as early as the second trimester, Dr. Brill said.

Many of the mothers referred to the program don’t have a primary care clinician when they talk to Paola Beamon, RN, at Ohio State. Ms. Beamon reaches out to each referred patient over voicemail, a MyChart message, and even regular mail in hopes of helping them navigate the postpartum period. She also provides education on what a primary care clinician can offer new moms.

“Really, we’re pursuing these moms and doing everything we can so there’s less of a burden for them,” Ms. Beamon said. “A lot of them don’t even know what a primary care office does.”

One of the biggest perks to the program for new moms is that they don’t have to spend time and money traveling to a different doctor’s office, take time off work, or secure childcare in order to schedule a separate appointment for themselves, she said.

The program, which receives funding from the university and the state, even helps women get bus passes to a doctor’s appointment if needed.

Dyad programs targeting women with substance abuse disorders or mental health conditions have existed for many years. But catering to women with gestational diabetes or other medical conditions appears to be new. In part, Dr. Venkataramani said, because scheduling and space can be big hurdles to launch such a program, as well as finding doctors who can care for both baby and mother.

“There are logistical challenges to even doing this that makes it less common,” she said.

Dr. Brill said she is not aware of any other programs that are structured like the tandem care clinic at Ohio State. She hopes, however, that the program can be a model for other hospital systems to consider, and she is working to expand the program regionally. Her team is collecting data – including on the best way to schedule patients – to help other clinics develop something similar. 

“We really want to leverage that expertise to make it easier for moms to get care with their infants and remove barriers to care,” she said.

A version of this article first appeared on Medscape.com.

Mindi Rosen met Seuli Brill, MD, at just the right time. 

Ms. Rosen’s firstborn son was in the neointensive natal unit at The Ohio State University Wexner Medical Center in Columbus, and she didn’t have a pediatrician picked out yet for the baby. Nor did she have a primary care physician who could help her manage the gestational diabetes she developed during her pregnancy.

Dr. Brill, a clinical associate professor of internal medicine and pediatrics at Ohio State, suggested Ms. Rosen visit her at the new clinic she was piloting in Columbus. There, she provided pediatric care for newborns and primary care for mothers who had developed gestational diabetes.  

“I looked at my husband, my husband looked at me, and I said: ‘Why not?’ “ Ms. Rosen, 38, recalled of that 2019 meeting. “I’m so glad she walked in at that moment.”

The mother of two is still part of the rapidly growing program at the medical facility that provides care for more than 200 mothers and babies.

Launched in 2018, the clinic – called the Multi-Modal Maternal Infant Perinatal Outpatient Delivery System, or “Momi Pods,” started with a focus  on helping women with gestational diabetes, which occurs in up to 10% of pregnancies.

The program allows moms to book regular checkups for their baby, and then a follow-up appointment immediately after for themselves. Women are seen for the first 1,000 days (just under 3 years) after giving birth.

The idea was simple. Dr. Brill wanted to develop a more formalized program for the work she was already doing as a primary care physician and pediatrician. At the time, she was fielding referrals from specialists for young women who didn’t have a physician. She’d often develop a relationship with the patient over the years, go on to help oversee their care during pregnancy, then new mothers would select her as their newborn’s pediatrician.

“I would have a relationship with the mom when they did have the newborn, and then I would see the baby because I’m a pediatrician,” Dr. Brill said.

Dr. Brill was serving on the Ohio Gestational Diabetes Mellitus Collaborative, a state-backed program that aims to raise awareness about the condition and encourage more preventative care for patients. She presented her proposal to launch the program to the Ohio Department of Medicaid, which helped to fund the pilot.

The idea, she hoped, would improve postpartum follow-up care for mothers diagnosed with the condition. 

Follow-up care is especially important for women who develop gestational diabetes because the condition raises their lifetime risk of developing type 2 diabetes up to 10-fold. 

Yet most of those mothers don’t get the appropriate follow-up care during the crucial postpartum period, said Maya Subbalakshmi Venkataramani, MD, MPH, an assistant professor of medicine at Johns Hopkins University in Baltimore, who has researched parental care. 

“Things get very busy after you have a child. There’s just the general logistics of a mom having to take care of a newborn and thinking about themselves,” Dr. Venkataramani, a primary care clinician and pediatrician, said. “A lot of parents in general may not put a lot of emphasis on their own health.”

Seeking care may be especially difficult for low-income mothers who might not have consistent health care coverage, she added.

In fact, only half of women who developed gestational diabetes received primary follow-up care, according to a study published in JAMA Network Open. The study, which examined more than 280,000 insurance claims between 2015 and 2018, found only 36% of women with gestational diabetes received the recommended blood glucose testing in the first 12 weeks of the postpartum period.

In the Momi Pods program, Dr. Brill checked in on Ms. Rosen’s gestational diabetes regularly during pediatric office visits for her newborn’s care. Ms. Rosen said whenever she brought her baby in for a visit during the postpartum period, Dr. Brill measured her blood sugar. 

Dr. Brill and her team also asked how Ms. Rosen was doing physically and mentally during each visit. The screenings helped to catch a bout of postpartum depression Ms. Rosen experienced after the birth of her first son.

“I thought it was great, because honestly as a new mom I wouldn’t have followed up with myself so much,” Ms. Rosen said. “Every time you went into the doctor appointments, they’d ask you how you are doing. As a new mom, it’s so much easier to do it at the same time.”

Those who participate in the program are also more likely to complete postpartum visits with their ob.gyn. (95% vs. 58%, respectively; P < .001) than those who don’t participate, according to research Dr. Brill and colleagues published.

Dr. Brill began expanding the program’s reach nearly 2 years after its launch, targeting the services for women who are at risk for poor postpartum outcomes, including those with a history of depression, preterm labor, diabetes and congenital heart disease. Ob.gyns. in Ohio State’s network can refer their patients to the program, which now has 43 doctors trained to provide primary and pediatric care through Momi Pods. Soon-to-be moms can be referred to the program as early as the second trimester, Dr. Brill said.

Many of the mothers referred to the program don’t have a primary care clinician when they talk to Paola Beamon, RN, at Ohio State. Ms. Beamon reaches out to each referred patient over voicemail, a MyChart message, and even regular mail in hopes of helping them navigate the postpartum period. She also provides education on what a primary care clinician can offer new moms.

“Really, we’re pursuing these moms and doing everything we can so there’s less of a burden for them,” Ms. Beamon said. “A lot of them don’t even know what a primary care office does.”

One of the biggest perks to the program for new moms is that they don’t have to spend time and money traveling to a different doctor’s office, take time off work, or secure childcare in order to schedule a separate appointment for themselves, she said.

The program, which receives funding from the university and the state, even helps women get bus passes to a doctor’s appointment if needed.

Dyad programs targeting women with substance abuse disorders or mental health conditions have existed for many years. But catering to women with gestational diabetes or other medical conditions appears to be new. In part, Dr. Venkataramani said, because scheduling and space can be big hurdles to launch such a program, as well as finding doctors who can care for both baby and mother.

“There are logistical challenges to even doing this that makes it less common,” she said.

Dr. Brill said she is not aware of any other programs that are structured like the tandem care clinic at Ohio State. She hopes, however, that the program can be a model for other hospital systems to consider, and she is working to expand the program regionally. Her team is collecting data – including on the best way to schedule patients – to help other clinics develop something similar. 

“We really want to leverage that expertise to make it easier for moms to get care with their infants and remove barriers to care,” she said.

A version of this article first appeared on Medscape.com.

Mindi Rosen met Seuli Brill, MD, at just the right time. 

Ms. Rosen’s firstborn son was in the neointensive natal unit at The Ohio State University Wexner Medical Center in Columbus, and she didn’t have a pediatrician picked out yet for the baby. Nor did she have a primary care physician who could help her manage the gestational diabetes she developed during her pregnancy.

Dr. Brill, a clinical associate professor of internal medicine and pediatrics at Ohio State, suggested Ms. Rosen visit her at the new clinic she was piloting in Columbus. There, she provided pediatric care for newborns and primary care for mothers who had developed gestational diabetes.  

“I looked at my husband, my husband looked at me, and I said: ‘Why not?’ “ Ms. Rosen, 38, recalled of that 2019 meeting. “I’m so glad she walked in at that moment.”

The mother of two is still part of the rapidly growing program at the medical facility that provides care for more than 200 mothers and babies.

Launched in 2018, the clinic – called the Multi-Modal Maternal Infant Perinatal Outpatient Delivery System, or “Momi Pods,” started with a focus  on helping women with gestational diabetes, which occurs in up to 10% of pregnancies.

The program allows moms to book regular checkups for their baby, and then a follow-up appointment immediately after for themselves. Women are seen for the first 1,000 days (just under 3 years) after giving birth.

The idea was simple. Dr. Brill wanted to develop a more formalized program for the work she was already doing as a primary care physician and pediatrician. At the time, she was fielding referrals from specialists for young women who didn’t have a physician. She’d often develop a relationship with the patient over the years, go on to help oversee their care during pregnancy, then new mothers would select her as their newborn’s pediatrician.

“I would have a relationship with the mom when they did have the newborn, and then I would see the baby because I’m a pediatrician,” Dr. Brill said.

Dr. Brill was serving on the Ohio Gestational Diabetes Mellitus Collaborative, a state-backed program that aims to raise awareness about the condition and encourage more preventative care for patients. She presented her proposal to launch the program to the Ohio Department of Medicaid, which helped to fund the pilot.

The idea, she hoped, would improve postpartum follow-up care for mothers diagnosed with the condition. 

Follow-up care is especially important for women who develop gestational diabetes because the condition raises their lifetime risk of developing type 2 diabetes up to 10-fold. 

Yet most of those mothers don’t get the appropriate follow-up care during the crucial postpartum period, said Maya Subbalakshmi Venkataramani, MD, MPH, an assistant professor of medicine at Johns Hopkins University in Baltimore, who has researched parental care. 

“Things get very busy after you have a child. There’s just the general logistics of a mom having to take care of a newborn and thinking about themselves,” Dr. Venkataramani, a primary care clinician and pediatrician, said. “A lot of parents in general may not put a lot of emphasis on their own health.”

Seeking care may be especially difficult for low-income mothers who might not have consistent health care coverage, she added.

In fact, only half of women who developed gestational diabetes received primary follow-up care, according to a study published in JAMA Network Open. The study, which examined more than 280,000 insurance claims between 2015 and 2018, found only 36% of women with gestational diabetes received the recommended blood glucose testing in the first 12 weeks of the postpartum period.

In the Momi Pods program, Dr. Brill checked in on Ms. Rosen’s gestational diabetes regularly during pediatric office visits for her newborn’s care. Ms. Rosen said whenever she brought her baby in for a visit during the postpartum period, Dr. Brill measured her blood sugar. 

Dr. Brill and her team also asked how Ms. Rosen was doing physically and mentally during each visit. The screenings helped to catch a bout of postpartum depression Ms. Rosen experienced after the birth of her first son.

“I thought it was great, because honestly as a new mom I wouldn’t have followed up with myself so much,” Ms. Rosen said. “Every time you went into the doctor appointments, they’d ask you how you are doing. As a new mom, it’s so much easier to do it at the same time.”

Those who participate in the program are also more likely to complete postpartum visits with their ob.gyn. (95% vs. 58%, respectively; P < .001) than those who don’t participate, according to research Dr. Brill and colleagues published.

Dr. Brill began expanding the program’s reach nearly 2 years after its launch, targeting the services for women who are at risk for poor postpartum outcomes, including those with a history of depression, preterm labor, diabetes and congenital heart disease. Ob.gyns. in Ohio State’s network can refer their patients to the program, which now has 43 doctors trained to provide primary and pediatric care through Momi Pods. Soon-to-be moms can be referred to the program as early as the second trimester, Dr. Brill said.

Many of the mothers referred to the program don’t have a primary care clinician when they talk to Paola Beamon, RN, at Ohio State. Ms. Beamon reaches out to each referred patient over voicemail, a MyChart message, and even regular mail in hopes of helping them navigate the postpartum period. She also provides education on what a primary care clinician can offer new moms.

“Really, we’re pursuing these moms and doing everything we can so there’s less of a burden for them,” Ms. Beamon said. “A lot of them don’t even know what a primary care office does.”

One of the biggest perks to the program for new moms is that they don’t have to spend time and money traveling to a different doctor’s office, take time off work, or secure childcare in order to schedule a separate appointment for themselves, she said.

The program, which receives funding from the university and the state, even helps women get bus passes to a doctor’s appointment if needed.

Dyad programs targeting women with substance abuse disorders or mental health conditions have existed for many years. But catering to women with gestational diabetes or other medical conditions appears to be new. In part, Dr. Venkataramani said, because scheduling and space can be big hurdles to launch such a program, as well as finding doctors who can care for both baby and mother.

“There are logistical challenges to even doing this that makes it less common,” she said.

Dr. Brill said she is not aware of any other programs that are structured like the tandem care clinic at Ohio State. She hopes, however, that the program can be a model for other hospital systems to consider, and she is working to expand the program regionally. Her team is collecting data – including on the best way to schedule patients – to help other clinics develop something similar. 

“We really want to leverage that expertise to make it easier for moms to get care with their infants and remove barriers to care,” she said.

A version of this article first appeared on Medscape.com.

Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.

While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.

Overview of online resources and navigating coverage

The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.

The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.

Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.

“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”

To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.

Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.

Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.

Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.

When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.

Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.

“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”

Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
 

Learning CGM through first-hand experience

Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.

“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”

Courtesy Dr. Neil Skolnik

Encouraging patients to start CGM

Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.

“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.

Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.

“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”

Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.

Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.

While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.

Overview of online resources and navigating coverage

The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.

The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.

Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.

“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”

To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.

Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.

Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.

Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.

When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.

Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.

“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”

Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
 

Learning CGM through first-hand experience

Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.

“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”

Courtesy Dr. Neil Skolnik

Encouraging patients to start CGM

Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.

“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.

Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.

“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”

Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.

Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.

While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.

Overview of online resources and navigating coverage

The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.

The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.

Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.

“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”

To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.

Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.

Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.

Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.

When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.

Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.

“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”

Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
 

Learning CGM through first-hand experience

Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.

“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”

Courtesy Dr. Neil Skolnik

Encouraging patients to start CGM

Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.

“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.

Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.

“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”

Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.

Treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease, new research suggests.

Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.

However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.

“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.

However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.

This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.

The results were published online in Neurology.
 

Dose-response relationship

Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.

This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.

Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.

Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.

Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.

There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).

A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
 

Several limitations

The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).

The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.

The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).

“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.

However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.

The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.

There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
 

More data needed

In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”

However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.

They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.

They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.

“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.

For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.

The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease, new research suggests.

Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.

However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.

“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.

However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.

This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.

The results were published online in Neurology.
 

Dose-response relationship

Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.

This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.

Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.

Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.

Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.

There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).

A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
 

Several limitations

The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).

The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.

The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).

“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.

However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.

The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.

There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
 

More data needed

In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”

However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.

They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.

They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.

“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.

For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.

The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease, new research suggests.

Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.

However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.

“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.

However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.

This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.

The results were published online in Neurology.
 

Dose-response relationship

Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.

This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.

Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.

Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.

Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.

There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).

A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
 

Several limitations

The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).

The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.

The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).

“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.

However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.

The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.

There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
 

More data needed

In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”

However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.

They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.

They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.

“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.

For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.

The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The increased risk for diabetes following COVID-19 infection has persisted into the Omicron era, but vaccination against SARS-CoV-2 appears to diminish that likelihood, new data suggest.

The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.

Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.

However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.

“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.

“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.

Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”

The findings were published online in JAMA Network Open.

Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.

Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.

The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).

Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).

The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).

However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.

There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.

Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”

He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”

This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.

A version of this article originally appeared on Medscape.com.

The increased risk for diabetes following COVID-19 infection has persisted into the Omicron era, but vaccination against SARS-CoV-2 appears to diminish that likelihood, new data suggest.

The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.

Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.

However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.

“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.

“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.

Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”

The findings were published online in JAMA Network Open.

Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.

Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.

The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).

Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).

The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).

However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.

There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.

Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”

He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”

This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.

A version of this article originally appeared on Medscape.com.

The increased risk for diabetes following COVID-19 infection has persisted into the Omicron era, but vaccination against SARS-CoV-2 appears to diminish that likelihood, new data suggest.

The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.

Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.

However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.

“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.

“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.

Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”

The findings were published online in JAMA Network Open.

Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.

Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.

The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).

Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).

The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).

However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.

There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.

Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”

He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”

This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.

A version of this article originally appeared on Medscape.com.

Type 2 diabetes (T2D) is a chronic, progressive disease marked by ongoing decline in insulin sensitivity and beta-cell function over time. Clinical trials have shown that lowering A1C to ∼7.0% (53 mmol/mol), especially after an early diagnosis, can markedly reduce the long-term complications of T2D. Metformin has become the generally recommended first therapeutic agent in treating T2D due to the drug’s long-term experience, effectiveness, and avoidance of hypoglycemia or weight gain. However, it is clear that additional agents are necessary to regain glucose control when metformin eventually fails due to the progressive nature of the disease.

Insufficient data on comparative efficacy and durability of effect has led to uncertainty in recommendations for the preferred second agent. Comparative effectiveness has been reported primarily in industry-sponsored trials of relatively short duration. With this in mind, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. This landmark, randomized controlled study was initiated in 2013, enrolling patients on metformin alone within 10 years of diagnosis of T2D. It involved 36 research sites in the United States with a mean follow-up of 5 years. The participants were randomized to adding a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin), a sulfonylurea (glimepiride), basal insulin (glargine), or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) (liraglutide), with the primary outcome being time to A1C over 7.0%.

The GRADE study was unique in several ways: its size, scope, length, and the fact that the financial support and design planning stemmed from a U34 planning grant from the NIDDK. The study population of 5047 participants was very diverse, reflecting the population affected by T2D. A mix of racial and ethnic groups were represented, including 19.8% Black participants and 18.6% Hispanic participants. It is unlikely that a similar comparative effectiveness trial of pharmacologic treatment of T2D will be performed again in the future, considering the high costs and length of time required for such a study amid the dynamic drug development environment today. In fact, the final implementation of study results is somewhat complicated by the subsequent approval of GLP-1 RAs of greater efficacy, weight loss, and convenience, as well as sodium-glucose cotransporter 2 (SGLT2) inhibitors and, most recently, a dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist (tirzepatide). Many of these newer agents have demonstrated nonglycemic benefits, such as reduced risk of cardiovascular (CV) events or reduced progression of renal disease. The findings from the GRADE study, however, did provide important insight on the long-term management of T2D.

The GRADE study was the first to compare the efficacy of 4 US Food and Drug Administration–approved drugs for T2D in maintaining blood glucose levels for the longest amount of time in patients with T2D. It also monitored microvascular complications, CV events, and adverse drug effects.

An important message of the study that may be overlooked is that all of the studied agents’ ability to maintain an A1C under 7.0% was quite low—as 71% of all participants reached the primary outcome by 5 years; the best results for a group were 67% for glargine and 68% for liraglutide. In general, the results showed that liraglutide and insulin glargine were superior to glimepiride and sitagliptin in controlling blood sugars. They provided approximately 6 months’ more time with blood glucose levels in the desired range compared with sitagliptin, which was shown to provide the least amount of time in maintaining glucose levels. Fifty-five percent of the sitagliptin group experienced the primary outcome at 1 year. Sitagliptin was particularly ineffective for the patient subgroup with an A1C at baseline of 7.8% or higher, where 70% reached the primary outcome in 1 year. The results were uniform regarding age, race, sex, and ethnicity of the trial participants. The intention-to-treat design of the study limits the conclusions about A1C differences, as failure to maintain an A1C under 7.5% required addition of prandial insulin for the glargine group and the addition of glargine to the other 3 groups. Although subjects receiving glargine had an initial glucose-lowering effect that was less than that seen with liraglutide, the ability to keep titrating the glargine likely had an impact on the long-term benefit of that agent. When the glargine group neared or in some cases even passed the secondary outcome A1C level of 7.5%, the basal insulin was increased to lower the A1C, sometimes even when the protocol would recommend adding prandial insulin.  

The study was not powered specifically for determining the relative risk of CV events. However, there was some evidence that liraglutide was associated with lower CV risk than the other 3 agents by about 30%. There was no difference in microvascular risk among the agents in this study of relatively short-term disease. Side effects were not a major problem and no different than expected. Glargine and glimepiride were associated with less weight loss, while liraglutide had a particular benefit on weight. Glimepiride is associated with significantly more frequent incidents of severe hypoglycemia, though the rates of severe hypoglycemia were quite low. Liraglutide users reported significantly higher rates of nausea and had a higher early drop-out rate, but did not show a difference in continued use by the end of the study.  

In summary, the GRADE trial confirmed that glucose control in T2D is a progressive problem, as the addition of all 4 classes of medication failed to keep most patients in the target glucose range. However, basal insulin and GLP-1 RAs outperformed the other 2 classes. Sitagliptin has the poorest metabolic profile. One could argue that, based on overall metabolic control and concomitant weight benefits, less need for glucose monitoring, simple titration, apparent CV benefit, and insignificant hypoglycemia, GLP-1 RAs offer the best option as an agent to add to metformin. This conclusion is fortified by the fact that the agent used to represent this class in the study appears to be less effective in reducing glucose and weight and offers less convenience than the newer, once-weekly GLP-RAs available today.   

Type 2 diabetes (T2D) is a chronic, progressive disease marked by ongoing decline in insulin sensitivity and beta-cell function over time. Clinical trials have shown that lowering A1C to ∼7.0% (53 mmol/mol), especially after an early diagnosis, can markedly reduce the long-term complications of T2D. Metformin has become the generally recommended first therapeutic agent in treating T2D due to the drug’s long-term experience, effectiveness, and avoidance of hypoglycemia or weight gain. However, it is clear that additional agents are necessary to regain glucose control when metformin eventually fails due to the progressive nature of the disease.

Insufficient data on comparative efficacy and durability of effect has led to uncertainty in recommendations for the preferred second agent. Comparative effectiveness has been reported primarily in industry-sponsored trials of relatively short duration. With this in mind, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. This landmark, randomized controlled study was initiated in 2013, enrolling patients on metformin alone within 10 years of diagnosis of T2D. It involved 36 research sites in the United States with a mean follow-up of 5 years. The participants were randomized to adding a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin), a sulfonylurea (glimepiride), basal insulin (glargine), or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) (liraglutide), with the primary outcome being time to A1C over 7.0%.

The GRADE study was unique in several ways: its size, scope, length, and the fact that the financial support and design planning stemmed from a U34 planning grant from the NIDDK. The study population of 5047 participants was very diverse, reflecting the population affected by T2D. A mix of racial and ethnic groups were represented, including 19.8% Black participants and 18.6% Hispanic participants. It is unlikely that a similar comparative effectiveness trial of pharmacologic treatment of T2D will be performed again in the future, considering the high costs and length of time required for such a study amid the dynamic drug development environment today. In fact, the final implementation of study results is somewhat complicated by the subsequent approval of GLP-1 RAs of greater efficacy, weight loss, and convenience, as well as sodium-glucose cotransporter 2 (SGLT2) inhibitors and, most recently, a dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist (tirzepatide). Many of these newer agents have demonstrated nonglycemic benefits, such as reduced risk of cardiovascular (CV) events or reduced progression of renal disease. The findings from the GRADE study, however, did provide important insight on the long-term management of T2D.

The GRADE study was the first to compare the efficacy of 4 US Food and Drug Administration–approved drugs for T2D in maintaining blood glucose levels for the longest amount of time in patients with T2D. It also monitored microvascular complications, CV events, and adverse drug effects.

An important message of the study that may be overlooked is that all of the studied agents’ ability to maintain an A1C under 7.0% was quite low—as 71% of all participants reached the primary outcome by 5 years; the best results for a group were 67% for glargine and 68% for liraglutide. In general, the results showed that liraglutide and insulin glargine were superior to glimepiride and sitagliptin in controlling blood sugars. They provided approximately 6 months’ more time with blood glucose levels in the desired range compared with sitagliptin, which was shown to provide the least amount of time in maintaining glucose levels. Fifty-five percent of the sitagliptin group experienced the primary outcome at 1 year. Sitagliptin was particularly ineffective for the patient subgroup with an A1C at baseline of 7.8% or higher, where 70% reached the primary outcome in 1 year. The results were uniform regarding age, race, sex, and ethnicity of the trial participants. The intention-to-treat design of the study limits the conclusions about A1C differences, as failure to maintain an A1C under 7.5% required addition of prandial insulin for the glargine group and the addition of glargine to the other 3 groups. Although subjects receiving glargine had an initial glucose-lowering effect that was less than that seen with liraglutide, the ability to keep titrating the glargine likely had an impact on the long-term benefit of that agent. When the glargine group neared or in some cases even passed the secondary outcome A1C level of 7.5%, the basal insulin was increased to lower the A1C, sometimes even when the protocol would recommend adding prandial insulin.  

The study was not powered specifically for determining the relative risk of CV events. However, there was some evidence that liraglutide was associated with lower CV risk than the other 3 agents by about 30%. There was no difference in microvascular risk among the agents in this study of relatively short-term disease. Side effects were not a major problem and no different than expected. Glargine and glimepiride were associated with less weight loss, while liraglutide had a particular benefit on weight. Glimepiride is associated with significantly more frequent incidents of severe hypoglycemia, though the rates of severe hypoglycemia were quite low. Liraglutide users reported significantly higher rates of nausea and had a higher early drop-out rate, but did not show a difference in continued use by the end of the study.  

In summary, the GRADE trial confirmed that glucose control in T2D is a progressive problem, as the addition of all 4 classes of medication failed to keep most patients in the target glucose range. However, basal insulin and GLP-1 RAs outperformed the other 2 classes. Sitagliptin has the poorest metabolic profile. One could argue that, based on overall metabolic control and concomitant weight benefits, less need for glucose monitoring, simple titration, apparent CV benefit, and insignificant hypoglycemia, GLP-1 RAs offer the best option as an agent to add to metformin. This conclusion is fortified by the fact that the agent used to represent this class in the study appears to be less effective in reducing glucose and weight and offers less convenience than the newer, once-weekly GLP-RAs available today.   

Type 2 diabetes (T2D) is a chronic, progressive disease marked by ongoing decline in insulin sensitivity and beta-cell function over time. Clinical trials have shown that lowering A1C to ∼7.0% (53 mmol/mol), especially after an early diagnosis, can markedly reduce the long-term complications of T2D. Metformin has become the generally recommended first therapeutic agent in treating T2D due to the drug’s long-term experience, effectiveness, and avoidance of hypoglycemia or weight gain. However, it is clear that additional agents are necessary to regain glucose control when metformin eventually fails due to the progressive nature of the disease.

Insufficient data on comparative efficacy and durability of effect has led to uncertainty in recommendations for the preferred second agent. Comparative effectiveness has been reported primarily in industry-sponsored trials of relatively short duration. With this in mind, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. This landmark, randomized controlled study was initiated in 2013, enrolling patients on metformin alone within 10 years of diagnosis of T2D. It involved 36 research sites in the United States with a mean follow-up of 5 years. The participants were randomized to adding a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin), a sulfonylurea (glimepiride), basal insulin (glargine), or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) (liraglutide), with the primary outcome being time to A1C over 7.0%.

The GRADE study was unique in several ways: its size, scope, length, and the fact that the financial support and design planning stemmed from a U34 planning grant from the NIDDK. The study population of 5047 participants was very diverse, reflecting the population affected by T2D. A mix of racial and ethnic groups were represented, including 19.8% Black participants and 18.6% Hispanic participants. It is unlikely that a similar comparative effectiveness trial of pharmacologic treatment of T2D will be performed again in the future, considering the high costs and length of time required for such a study amid the dynamic drug development environment today. In fact, the final implementation of study results is somewhat complicated by the subsequent approval of GLP-1 RAs of greater efficacy, weight loss, and convenience, as well as sodium-glucose cotransporter 2 (SGLT2) inhibitors and, most recently, a dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist (tirzepatide). Many of these newer agents have demonstrated nonglycemic benefits, such as reduced risk of cardiovascular (CV) events or reduced progression of renal disease. The findings from the GRADE study, however, did provide important insight on the long-term management of T2D.

The GRADE study was the first to compare the efficacy of 4 US Food and Drug Administration–approved drugs for T2D in maintaining blood glucose levels for the longest amount of time in patients with T2D. It also monitored microvascular complications, CV events, and adverse drug effects.

An important message of the study that may be overlooked is that all of the studied agents’ ability to maintain an A1C under 7.0% was quite low—as 71% of all participants reached the primary outcome by 5 years; the best results for a group were 67% for glargine and 68% for liraglutide. In general, the results showed that liraglutide and insulin glargine were superior to glimepiride and sitagliptin in controlling blood sugars. They provided approximately 6 months’ more time with blood glucose levels in the desired range compared with sitagliptin, which was shown to provide the least amount of time in maintaining glucose levels. Fifty-five percent of the sitagliptin group experienced the primary outcome at 1 year. Sitagliptin was particularly ineffective for the patient subgroup with an A1C at baseline of 7.8% or higher, where 70% reached the primary outcome in 1 year. The results were uniform regarding age, race, sex, and ethnicity of the trial participants. The intention-to-treat design of the study limits the conclusions about A1C differences, as failure to maintain an A1C under 7.5% required addition of prandial insulin for the glargine group and the addition of glargine to the other 3 groups. Although subjects receiving glargine had an initial glucose-lowering effect that was less than that seen with liraglutide, the ability to keep titrating the glargine likely had an impact on the long-term benefit of that agent. When the glargine group neared or in some cases even passed the secondary outcome A1C level of 7.5%, the basal insulin was increased to lower the A1C, sometimes even when the protocol would recommend adding prandial insulin.  

The study was not powered specifically for determining the relative risk of CV events. However, there was some evidence that liraglutide was associated with lower CV risk than the other 3 agents by about 30%. There was no difference in microvascular risk among the agents in this study of relatively short-term disease. Side effects were not a major problem and no different than expected. Glargine and glimepiride were associated with less weight loss, while liraglutide had a particular benefit on weight. Glimepiride is associated with significantly more frequent incidents of severe hypoglycemia, though the rates of severe hypoglycemia were quite low. Liraglutide users reported significantly higher rates of nausea and had a higher early drop-out rate, but did not show a difference in continued use by the end of the study.  

In summary, the GRADE trial confirmed that glucose control in T2D is a progressive problem, as the addition of all 4 classes of medication failed to keep most patients in the target glucose range. However, basal insulin and GLP-1 RAs outperformed the other 2 classes. Sitagliptin has the poorest metabolic profile. One could argue that, based on overall metabolic control and concomitant weight benefits, less need for glucose monitoring, simple titration, apparent CV benefit, and insignificant hypoglycemia, GLP-1 RAs offer the best option as an agent to add to metformin. This conclusion is fortified by the fact that the agent used to represent this class in the study appears to be less effective in reducing glucose and weight and offers less convenience than the newer, once-weekly GLP-RAs available today.   

About two-thirds of people with type 1 diabetes in the United States have overweight or obesity, nearly the same proportion as Americans without diabetes, new nationwide survey data suggest.

What’s more, among people with overweight or obesity, those with type 1 diabetes are less likely to receive lifestyle recommendations from health care professionals than those with type 2 diabetes, and are less likely to actually engage in lifestyle weight management activities than others with overweight or obesity, with or without type 2 diabetes.

“Among U.S. adults with type 1 diabetes, the burden of overweight and obesity is substantial and remains poorly managed,” write Michael Fang, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues.

Their data, from the National Health Interview Survey (NHIS), were published online in Annals of Internal Medicine.

The need for insulin complicates weight management in people with type 1 diabetes because changes in diet and physical activity typically require adjustments to insulin timing and dosage to prevent hypoglycemia. There is little evidence to guide this for weight management, Dr. Fang and colleagues explain.

Consequently, “the lack of evidence for safe, effective methods of diet- and exercise-based weight control in people with type 1 diabetes may be keeping doctors from recommending such methods,” Dr. Fang said in a statement.

“Large clinical trials have been done in type 2 diabetes patients to establish guidelines for diet- and exercise-based weight management, and we now need something similar for type 1 diabetes patients.”  

Asked to comment, M. Sue Kirkman, MD, told this news organization: “The days when we could teach simple concepts about diabetes type like ‘those with type 1 are lean and those with type 2 are overweight’ are long gone. … Of concern, fewer adults with type 1 diabetes and overweight/obesity report that they are engaging in physical activity or caloric restriction than those without diabetes or those with type 2 diabetes.”

There are several likely reasons for the low rates of obesity/overweight lifestyle modification advice and implementation for those with type 1 diabetes, noted Dr. Kirkman, of the University of North Carolina at Chapel Hill, who coauthored joint American/European guidance on type 1 diabetes management.

“Medical visits are often primarily focused on glycemic management and complications screening, and we know that physicians in general are not very knowledgeable about how to counsel people – even those without diabetes – on weight loss. When you add in potential worries, real or not, about hypoglycemia, ketosis with carbohydrate restriction … it’s no wonder that this may not be addressed in busy visits.”

She also observed, “In years of going to diabetes meetings, I’ve noticed occasional sessions on managing ‘elite athletes’ with type 1 diabetes, but rarely are there sessions on how to counsel people about everyday healthy living.”
 

Many with type 1 diabetes have overweight/obesity

Dr. Fang and colleagues analyzed NHIS data for the years 2016, 2017, 2019, 2020, and 2021, when diabetes subtype data were available, for 128,571 adults. Diabetes type and height/weight data were self-reported. In the 2016, 2017, and 2020 surveys, participants were asked whether their physicians had recommended increasing physical activity and/or reducing calorie or fat consumption, and whether they were currently engaging in those activities.

The study population comprised 733 people with type 1 diabetes, 12,397 with type 2 diabetes, and 115,441 without diabetes. The proportions with overweight (body mass index, 25 to < 30 kg/m²) or obesity (≥ 30 kg/m²) were 62% among those with type 1 diabetes and 64% among those without diabetes, compared with 86% among those with type 2 diabetes.

Among those with overweight or obesity, the proportions who reported having received lifestyle recommendations were greatest among those with type 2 diabetes and least among those without diabetes, with the type 1 diabetes group in the middle.

After adjustment for age, sex, and race/ethnicity, the adjusted prevalence of receiving a provider recommendation to increase physical activity was 60% for those with type 2 diabetes, 54% for type 1 diabetes, and 44% for those without diabetes. Proportions for receiving recommendations for reducing fat/caloric intake were similar, at 60%, 51%, and 41%, respectively.

The proportions who reported actually engaging in lifestyle activities for weight management were lowest among those with type 1 diabetes, with 52% and 56% of them reporting having increased their physical activity and reducing fat/calories, respectively, compared with proportions ranging from 56% to 63% among the other two groups.

Regarding those findings, Dr. Kirkman commented, “In addition to the factors regarding physician interactions, people with type 1 diabetes may see this as a lower-priority health issue after years of being told that glucose control is the main priority.”

“I also wonder if the many, many tasks people with type 1 diabetes must do every day to manage their diabetes – along with other life issues all adults face – mean that there is just too much on the plate to add more lifestyle changes,” she added.

Asked about the potential for off-label use of glucagonlike peptide–1 agonists for weight management for people with type 1 diabetes, Dr. Kirkman said they could probably help some patients. However, she also pointed to two clinical trials in which liraglutide added to insulin therapy helped with glycemic control and weight reduction, but also increased the risk for hypoglycemia and diabetic ketoacidosis.

“It’s really important that researchers engage with adults with type 1 diabetes to better understand the unique priorities and barriers they face in addressing body weight,” Dr. Kirkman said.

Senior study author Elizabeth Selvin, PhD, professor of epidemiology at the Bloomberg School, said in the statement: “Our study busts the myth that people with type 1 diabetes are not being affected by the global obesity epidemic. … These findings should be a wake-up call that we need to be aggressive in addressing the obesity epidemic in persons with type 1 diabetes.”

The study was funded by the U.S. National Institutes of Health. Dr. Fang and Dr. Kirkman have reported no relevant financial relationships. Dr. Selvin has reported receiving royalty payments from Wolters Kluwer for chapters and laboratory monographs in UpToDate. She also reports receiving honoraria for editorial work on journals published by the American Diabetes Association and European Association for the Study of Diabetes.

A version of this article originally appeared on Medscape.com.

About two-thirds of people with type 1 diabetes in the United States have overweight or obesity, nearly the same proportion as Americans without diabetes, new nationwide survey data suggest.

What’s more, among people with overweight or obesity, those with type 1 diabetes are less likely to receive lifestyle recommendations from health care professionals than those with type 2 diabetes, and are less likely to actually engage in lifestyle weight management activities than others with overweight or obesity, with or without type 2 diabetes.

“Among U.S. adults with type 1 diabetes, the burden of overweight and obesity is substantial and remains poorly managed,” write Michael Fang, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues.

Their data, from the National Health Interview Survey (NHIS), were published online in Annals of Internal Medicine.

The need for insulin complicates weight management in people with type 1 diabetes because changes in diet and physical activity typically require adjustments to insulin timing and dosage to prevent hypoglycemia. There is little evidence to guide this for weight management, Dr. Fang and colleagues explain.

Consequently, “the lack of evidence for safe, effective methods of diet- and exercise-based weight control in people with type 1 diabetes may be keeping doctors from recommending such methods,” Dr. Fang said in a statement.

“Large clinical trials have been done in type 2 diabetes patients to establish guidelines for diet- and exercise-based weight management, and we now need something similar for type 1 diabetes patients.”  

Asked to comment, M. Sue Kirkman, MD, told this news organization: “The days when we could teach simple concepts about diabetes type like ‘those with type 1 are lean and those with type 2 are overweight’ are long gone. … Of concern, fewer adults with type 1 diabetes and overweight/obesity report that they are engaging in physical activity or caloric restriction than those without diabetes or those with type 2 diabetes.”

There are several likely reasons for the low rates of obesity/overweight lifestyle modification advice and implementation for those with type 1 diabetes, noted Dr. Kirkman, of the University of North Carolina at Chapel Hill, who coauthored joint American/European guidance on type 1 diabetes management.

“Medical visits are often primarily focused on glycemic management and complications screening, and we know that physicians in general are not very knowledgeable about how to counsel people – even those without diabetes – on weight loss. When you add in potential worries, real or not, about hypoglycemia, ketosis with carbohydrate restriction … it’s no wonder that this may not be addressed in busy visits.”

She also observed, “In years of going to diabetes meetings, I’ve noticed occasional sessions on managing ‘elite athletes’ with type 1 diabetes, but rarely are there sessions on how to counsel people about everyday healthy living.”
 

Many with type 1 diabetes have overweight/obesity

Dr. Fang and colleagues analyzed NHIS data for the years 2016, 2017, 2019, 2020, and 2021, when diabetes subtype data were available, for 128,571 adults. Diabetes type and height/weight data were self-reported. In the 2016, 2017, and 2020 surveys, participants were asked whether their physicians had recommended increasing physical activity and/or reducing calorie or fat consumption, and whether they were currently engaging in those activities.

The study population comprised 733 people with type 1 diabetes, 12,397 with type 2 diabetes, and 115,441 without diabetes. The proportions with overweight (body mass index, 25 to < 30 kg/m²) or obesity (≥ 30 kg/m²) were 62% among those with type 1 diabetes and 64% among those without diabetes, compared with 86% among those with type 2 diabetes.

Among those with overweight or obesity, the proportions who reported having received lifestyle recommendations were greatest among those with type 2 diabetes and least among those without diabetes, with the type 1 diabetes group in the middle.

After adjustment for age, sex, and race/ethnicity, the adjusted prevalence of receiving a provider recommendation to increase physical activity was 60% for those with type 2 diabetes, 54% for type 1 diabetes, and 44% for those without diabetes. Proportions for receiving recommendations for reducing fat/caloric intake were similar, at 60%, 51%, and 41%, respectively.

The proportions who reported actually engaging in lifestyle activities for weight management were lowest among those with type 1 diabetes, with 52% and 56% of them reporting having increased their physical activity and reducing fat/calories, respectively, compared with proportions ranging from 56% to 63% among the other two groups.

Regarding those findings, Dr. Kirkman commented, “In addition to the factors regarding physician interactions, people with type 1 diabetes may see this as a lower-priority health issue after years of being told that glucose control is the main priority.”

“I also wonder if the many, many tasks people with type 1 diabetes must do every day to manage their diabetes – along with other life issues all adults face – mean that there is just too much on the plate to add more lifestyle changes,” she added.

Asked about the potential for off-label use of glucagonlike peptide–1 agonists for weight management for people with type 1 diabetes, Dr. Kirkman said they could probably help some patients. However, she also pointed to two clinical trials in which liraglutide added to insulin therapy helped with glycemic control and weight reduction, but also increased the risk for hypoglycemia and diabetic ketoacidosis.

“It’s really important that researchers engage with adults with type 1 diabetes to better understand the unique priorities and barriers they face in addressing body weight,” Dr. Kirkman said.

Senior study author Elizabeth Selvin, PhD, professor of epidemiology at the Bloomberg School, said in the statement: “Our study busts the myth that people with type 1 diabetes are not being affected by the global obesity epidemic. … These findings should be a wake-up call that we need to be aggressive in addressing the obesity epidemic in persons with type 1 diabetes.”

The study was funded by the U.S. National Institutes of Health. Dr. Fang and Dr. Kirkman have reported no relevant financial relationships. Dr. Selvin has reported receiving royalty payments from Wolters Kluwer for chapters and laboratory monographs in UpToDate. She also reports receiving honoraria for editorial work on journals published by the American Diabetes Association and European Association for the Study of Diabetes.

A version of this article originally appeared on Medscape.com.

About two-thirds of people with type 1 diabetes in the United States have overweight or obesity, nearly the same proportion as Americans without diabetes, new nationwide survey data suggest.

What’s more, among people with overweight or obesity, those with type 1 diabetes are less likely to receive lifestyle recommendations from health care professionals than those with type 2 diabetes, and are less likely to actually engage in lifestyle weight management activities than others with overweight or obesity, with or without type 2 diabetes.

“Among U.S. adults with type 1 diabetes, the burden of overweight and obesity is substantial and remains poorly managed,” write Michael Fang, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues.

Their data, from the National Health Interview Survey (NHIS), were published online in Annals of Internal Medicine.

The need for insulin complicates weight management in people with type 1 diabetes because changes in diet and physical activity typically require adjustments to insulin timing and dosage to prevent hypoglycemia. There is little evidence to guide this for weight management, Dr. Fang and colleagues explain.

Consequently, “the lack of evidence for safe, effective methods of diet- and exercise-based weight control in people with type 1 diabetes may be keeping doctors from recommending such methods,” Dr. Fang said in a statement.

“Large clinical trials have been done in type 2 diabetes patients to establish guidelines for diet- and exercise-based weight management, and we now need something similar for type 1 diabetes patients.”  

Asked to comment, M. Sue Kirkman, MD, told this news organization: “The days when we could teach simple concepts about diabetes type like ‘those with type 1 are lean and those with type 2 are overweight’ are long gone. … Of concern, fewer adults with type 1 diabetes and overweight/obesity report that they are engaging in physical activity or caloric restriction than those without diabetes or those with type 2 diabetes.”

There are several likely reasons for the low rates of obesity/overweight lifestyle modification advice and implementation for those with type 1 diabetes, noted Dr. Kirkman, of the University of North Carolina at Chapel Hill, who coauthored joint American/European guidance on type 1 diabetes management.

“Medical visits are often primarily focused on glycemic management and complications screening, and we know that physicians in general are not very knowledgeable about how to counsel people – even those without diabetes – on weight loss. When you add in potential worries, real or not, about hypoglycemia, ketosis with carbohydrate restriction … it’s no wonder that this may not be addressed in busy visits.”

She also observed, “In years of going to diabetes meetings, I’ve noticed occasional sessions on managing ‘elite athletes’ with type 1 diabetes, but rarely are there sessions on how to counsel people about everyday healthy living.”
 

Many with type 1 diabetes have overweight/obesity

Dr. Fang and colleagues analyzed NHIS data for the years 2016, 2017, 2019, 2020, and 2021, when diabetes subtype data were available, for 128,571 adults. Diabetes type and height/weight data were self-reported. In the 2016, 2017, and 2020 surveys, participants were asked whether their physicians had recommended increasing physical activity and/or reducing calorie or fat consumption, and whether they were currently engaging in those activities.

The study population comprised 733 people with type 1 diabetes, 12,397 with type 2 diabetes, and 115,441 without diabetes. The proportions with overweight (body mass index, 25 to < 30 kg/m²) or obesity (≥ 30 kg/m²) were 62% among those with type 1 diabetes and 64% among those without diabetes, compared with 86% among those with type 2 diabetes.

Among those with overweight or obesity, the proportions who reported having received lifestyle recommendations were greatest among those with type 2 diabetes and least among those without diabetes, with the type 1 diabetes group in the middle.

After adjustment for age, sex, and race/ethnicity, the adjusted prevalence of receiving a provider recommendation to increase physical activity was 60% for those with type 2 diabetes, 54% for type 1 diabetes, and 44% for those without diabetes. Proportions for receiving recommendations for reducing fat/caloric intake were similar, at 60%, 51%, and 41%, respectively.

The proportions who reported actually engaging in lifestyle activities for weight management were lowest among those with type 1 diabetes, with 52% and 56% of them reporting having increased their physical activity and reducing fat/calories, respectively, compared with proportions ranging from 56% to 63% among the other two groups.

Regarding those findings, Dr. Kirkman commented, “In addition to the factors regarding physician interactions, people with type 1 diabetes may see this as a lower-priority health issue after years of being told that glucose control is the main priority.”

“I also wonder if the many, many tasks people with type 1 diabetes must do every day to manage their diabetes – along with other life issues all adults face – mean that there is just too much on the plate to add more lifestyle changes,” she added.

Asked about the potential for off-label use of glucagonlike peptide–1 agonists for weight management for people with type 1 diabetes, Dr. Kirkman said they could probably help some patients. However, she also pointed to two clinical trials in which liraglutide added to insulin therapy helped with glycemic control and weight reduction, but also increased the risk for hypoglycemia and diabetic ketoacidosis.

“It’s really important that researchers engage with adults with type 1 diabetes to better understand the unique priorities and barriers they face in addressing body weight,” Dr. Kirkman said.

Senior study author Elizabeth Selvin, PhD, professor of epidemiology at the Bloomberg School, said in the statement: “Our study busts the myth that people with type 1 diabetes are not being affected by the global obesity epidemic. … These findings should be a wake-up call that we need to be aggressive in addressing the obesity epidemic in persons with type 1 diabetes.”

The study was funded by the U.S. National Institutes of Health. Dr. Fang and Dr. Kirkman have reported no relevant financial relationships. Dr. Selvin has reported receiving royalty payments from Wolters Kluwer for chapters and laboratory monographs in UpToDate. She also reports receiving honoraria for editorial work on journals published by the American Diabetes Association and European Association for the Study of Diabetes.

A version of this article originally appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

Middle-aged White women who had higher levels of some breakdown products of phthalates – a class of endocrine disrupting chemicals (EDCs), or “forever chemicals,” that act as plasticizers – had a significantly greater risk of developing type 2 diabetes over a 6-year period compared with other similar women.

However, this association was not seen among Black or Asian middle-aged women.

These findings from the Study of Women’s Health Across the Nation – Multipollutant Study (SWAN-MPS), by Mia Q. Peng, PhD, MPH, and colleagues, have been published online in the Journal of Clinical Endocrinology & Metabolism.

“Overall, our study has added some evidence to support the potential diabetogenic effects of phthalates, but it also highlights that much is still unknown about the metabolic effects of these chemicals,” the group noted.

“The apparent racial/ethnic differences in the associations between phthalates and incident diabetes should be investigated in future studies,” they cautioned.

Recruiting younger participants and observing them longer, they suggested, “will also help us understand the effects of phthalates on different stages of the diabetogenic process, including whether body fat gain is an important mediator.”
 

Phthalates are all around us

Low-molecular-weight phthalates are frequently added to personal care products, such as fragrance, nail polish, and some feminine hygiene products, as solvents, plasticizers, and fixatives, the researchers explained.

And high-molecular-weight phthalates are frequently added to polyvinyl chloride plastic products, such as plastic food packaging, clothing, and vinyl flooring, as plasticizers.

Phthalates have been hypothesized to contribute to the development of diabetes, but longitudinal evidence in humans was limited.

“Given widespread exposure to phthalates and the enormous costs of diabetes to individuals and societies, ongoing investments in the research on phthalates’ metabolic effects are warranted,” the researchers concluded.
 

Racial differences in phthalates and incident diabetes

“A new finding is that we observed some phthalates are associated with a higher risk of diabetes development, especially in White women [that] were not seen in Black or Asian women,” senior author Sung Kyun Park, ScD, MPH, of the University of Michigan, Ann Arbor, told this news organization.

“We were surprised to see the racial/ethnic differences,” added Dr. Peng, formerly of the University of Michigan and now at Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus.

A possible explanation is that “compared to White women, Black women develop diabetes at a younger age and are exposed to higher levels of several phthalates,” and this study excluded women who already had diabetes by midlife, she noted.

“Although our study was conducted in a cohort of women,” Dr. Park stressed, “we hope that our findings are not interpreted that only women should be concerned of phthalates. Our findings add to the current literature that phthalates may be a potential risk factor for type 2 diabetes.

“Certain phthalates are prohibited in children’s toys and child care articles,” Dr. Peng noted, as explained by the U.S. Consumer Product Safety Commission. In addition, a bill has been introduced in Congress to ban phthalates in food contact substances.

“If phthalates are removed from plastics and other consumer products,” she cautioned, “we do have to be careful in the process to avoid replacing them with some other potentially harmful chemicals.”

A well-known example of this type of “regrettable substitution,” Dr. Park added, “is ‘BPA-free’ plastics that replaced bisphenol A with other bisphenols such as bisphenol-F (BPF) or bisphenol-S (BPS). The product has a label of ‘BPA-free’, but those replaced chemicals turned out to be equally toxic. Science is slow to determine if a new chemical introduced to the market is safe and can replace a regulated chemical.”

And studies have shown that a diet rich in meat, fat, and ultraprocessed foods is associated with increased exposures to some phthalates, especially when the foods are obtained away from home, such as fast foods, Dr. Peng observed. In addition, some phthalates are added to personal care products such as fragrance.

“As a first step,” she said, “I think reducing consumption of ultraprocessed foods packaged in plastics may help reduce phthalate exposure.”

A 2020 report from the Endocrine Society and the International Pollutants Elimination Network (IPEN), titled, “Plastics, EDCs, and Health,” summarizes research on bisphenol A, per- and polyfluoroalkyl substances (PFAS), phthalates, and other EDCs that leach from plastics. The Endocrine Society website also has a link to a 2-page summary.  
 

Levels of 12 phthalate metabolites

Previously, the researchers reported how another class of “forever chemicals,” PFAS, were associated with risk of hypertension in a 17-year follow-up of middle-aged women in the SWAN study.

In the current study, they analyzed data from 1,308 women in SWAN-MPS who had been recruited at five study sites (Oakland, Calif; Los Angeles; Detroit; Pittsburgh; and Boston).

The women were between ages 42 and 52 years in 1996-1997 and self-identified as White, Black, Chinese, or Japanese.

They did not have diabetes in 1999-2000 and had sufficient urine samples for phthalate assessment then and midway through a 6-year follow-up.

The women were a median age of 49 years in 1999-2000. About half were White, 20% were Black, 13% were Chinese, and 15% were Japanese.

Researchers analyzed levels of 12 metabolites, chosen because their parent phthalates have been widely used in industry and commerce, and exposure to these phthalates is a national biomonitoring priority.

The measured phthalates were:

Three metabolites of low-molecular-weight phthalates:

• mono-ethyl phthalate (MEP)
• mono-n-butyl phthalate (MnBP)
• mono-isobutyl phthalate (MiBP)

Four metabolites of the high-molecular-weight phthalate di(2-ethylhexyl) phthalate (DEHP), which is of particular public health interest:

• mono(2-ethylhexyl) phthalate (MEHP)
• mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)
• mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)
• mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)

Five metabolites of other high-molecular-weight phthalates:

• monobenzyl phthalate (MBzP)
• monoisononyl phthalate (MiNP)
• mono-carboxyoctyl phthalate (MCOP)
• mono-carboxy-isononyl phthalate (MCNP)
• mono(3-carboxypropyl) phthalate (MCPP)

The researchers excluded MiNP from all analyses because it was detected in less than 1% of urine samples.

The different phthalate metabolites were detected in 84.8% of samples (MEHP) to 100% of samples (MnBP and MECPP).

Women who were younger, Black, current smokers, or obese generally had higher concentrations of phthalate metabolites.

Over 6 years, 61 women developed diabetes (an incidence rate of 8.1 per 1000 person-years).

Compared with other women, those with incident diabetes had significantly higher concentrations of all phthalate metabolites except DEHP metabolites and MCPP. 

Phthalates were not associated with incident diabetes in Black or Asian women.

However, among White women, each doubling of the concentrations of MiBP, MBzP, MCOP, MCNP, and MCCP was associated with a 30% to 63% higher incidence of diabetes (HR 1.30 for MCNP; HR 1.63 for MiBP).

The SWAN study was supported by the National Institutes of Health, Department of Health & Human Services, National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and SWAN Repository. The current study was supported by the National Center for Research Resources, National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. Dr. Peng was supported by an Interdisciplinary Research Training on Health and Aging grant from the NIA. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Middle-aged White women who had higher levels of some breakdown products of phthalates – a class of endocrine disrupting chemicals (EDCs), or “forever chemicals,” that act as plasticizers – had a significantly greater risk of developing type 2 diabetes over a 6-year period compared with other similar women.

However, this association was not seen among Black or Asian middle-aged women.

These findings from the Study of Women’s Health Across the Nation – Multipollutant Study (SWAN-MPS), by Mia Q. Peng, PhD, MPH, and colleagues, have been published online in the Journal of Clinical Endocrinology & Metabolism.

“Overall, our study has added some evidence to support the potential diabetogenic effects of phthalates, but it also highlights that much is still unknown about the metabolic effects of these chemicals,” the group noted.

“The apparent racial/ethnic differences in the associations between phthalates and incident diabetes should be investigated in future studies,” they cautioned.

Recruiting younger participants and observing them longer, they suggested, “will also help us understand the effects of phthalates on different stages of the diabetogenic process, including whether body fat gain is an important mediator.”
 

Phthalates are all around us

Low-molecular-weight phthalates are frequently added to personal care products, such as fragrance, nail polish, and some feminine hygiene products, as solvents, plasticizers, and fixatives, the researchers explained.

And high-molecular-weight phthalates are frequently added to polyvinyl chloride plastic products, such as plastic food packaging, clothing, and vinyl flooring, as plasticizers.

Phthalates have been hypothesized to contribute to the development of diabetes, but longitudinal evidence in humans was limited.

“Given widespread exposure to phthalates and the enormous costs of diabetes to individuals and societies, ongoing investments in the research on phthalates’ metabolic effects are warranted,” the researchers concluded.
 

Racial differences in phthalates and incident diabetes

“A new finding is that we observed some phthalates are associated with a higher risk of diabetes development, especially in White women [that] were not seen in Black or Asian women,” senior author Sung Kyun Park, ScD, MPH, of the University of Michigan, Ann Arbor, told this news organization.

“We were surprised to see the racial/ethnic differences,” added Dr. Peng, formerly of the University of Michigan and now at Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus.

A possible explanation is that “compared to White women, Black women develop diabetes at a younger age and are exposed to higher levels of several phthalates,” and this study excluded women who already had diabetes by midlife, she noted.

“Although our study was conducted in a cohort of women,” Dr. Park stressed, “we hope that our findings are not interpreted that only women should be concerned of phthalates. Our findings add to the current literature that phthalates may be a potential risk factor for type 2 diabetes.

“Certain phthalates are prohibited in children’s toys and child care articles,” Dr. Peng noted, as explained by the U.S. Consumer Product Safety Commission. In addition, a bill has been introduced in Congress to ban phthalates in food contact substances.

“If phthalates are removed from plastics and other consumer products,” she cautioned, “we do have to be careful in the process to avoid replacing them with some other potentially harmful chemicals.”

A well-known example of this type of “regrettable substitution,” Dr. Park added, “is ‘BPA-free’ plastics that replaced bisphenol A with other bisphenols such as bisphenol-F (BPF) or bisphenol-S (BPS). The product has a label of ‘BPA-free’, but those replaced chemicals turned out to be equally toxic. Science is slow to determine if a new chemical introduced to the market is safe and can replace a regulated chemical.”

And studies have shown that a diet rich in meat, fat, and ultraprocessed foods is associated with increased exposures to some phthalates, especially when the foods are obtained away from home, such as fast foods, Dr. Peng observed. In addition, some phthalates are added to personal care products such as fragrance.

“As a first step,” she said, “I think reducing consumption of ultraprocessed foods packaged in plastics may help reduce phthalate exposure.”

A 2020 report from the Endocrine Society and the International Pollutants Elimination Network (IPEN), titled, “Plastics, EDCs, and Health,” summarizes research on bisphenol A, per- and polyfluoroalkyl substances (PFAS), phthalates, and other EDCs that leach from plastics. The Endocrine Society website also has a link to a 2-page summary.  
 

Levels of 12 phthalate metabolites

Previously, the researchers reported how another class of “forever chemicals,” PFAS, were associated with risk of hypertension in a 17-year follow-up of middle-aged women in the SWAN study.

In the current study, they analyzed data from 1,308 women in SWAN-MPS who had been recruited at five study sites (Oakland, Calif; Los Angeles; Detroit; Pittsburgh; and Boston).

The women were between ages 42 and 52 years in 1996-1997 and self-identified as White, Black, Chinese, or Japanese.

They did not have diabetes in 1999-2000 and had sufficient urine samples for phthalate assessment then and midway through a 6-year follow-up.

The women were a median age of 49 years in 1999-2000. About half were White, 20% were Black, 13% were Chinese, and 15% were Japanese.

Researchers analyzed levels of 12 metabolites, chosen because their parent phthalates have been widely used in industry and commerce, and exposure to these phthalates is a national biomonitoring priority.

The measured phthalates were:

Three metabolites of low-molecular-weight phthalates:

• mono-ethyl phthalate (MEP)
• mono-n-butyl phthalate (MnBP)
• mono-isobutyl phthalate (MiBP)

Four metabolites of the high-molecular-weight phthalate di(2-ethylhexyl) phthalate (DEHP), which is of particular public health interest:

• mono(2-ethylhexyl) phthalate (MEHP)
• mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)
• mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)
• mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)

Five metabolites of other high-molecular-weight phthalates:

• monobenzyl phthalate (MBzP)
• monoisononyl phthalate (MiNP)
• mono-carboxyoctyl phthalate (MCOP)
• mono-carboxy-isononyl phthalate (MCNP)
• mono(3-carboxypropyl) phthalate (MCPP)

The researchers excluded MiNP from all analyses because it was detected in less than 1% of urine samples.

The different phthalate metabolites were detected in 84.8% of samples (MEHP) to 100% of samples (MnBP and MECPP).

Women who were younger, Black, current smokers, or obese generally had higher concentrations of phthalate metabolites.

Over 6 years, 61 women developed diabetes (an incidence rate of 8.1 per 1000 person-years).

Compared with other women, those with incident diabetes had significantly higher concentrations of all phthalate metabolites except DEHP metabolites and MCPP. 

Phthalates were not associated with incident diabetes in Black or Asian women.

However, among White women, each doubling of the concentrations of MiBP, MBzP, MCOP, MCNP, and MCCP was associated with a 30% to 63% higher incidence of diabetes (HR 1.30 for MCNP; HR 1.63 for MiBP).

The SWAN study was supported by the National Institutes of Health, Department of Health & Human Services, National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and SWAN Repository. The current study was supported by the National Center for Research Resources, National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. Dr. Peng was supported by an Interdisciplinary Research Training on Health and Aging grant from the NIA. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Middle-aged White women who had higher levels of some breakdown products of phthalates – a class of endocrine disrupting chemicals (EDCs), or “forever chemicals,” that act as plasticizers – had a significantly greater risk of developing type 2 diabetes over a 6-year period compared with other similar women.

However, this association was not seen among Black or Asian middle-aged women.

These findings from the Study of Women’s Health Across the Nation – Multipollutant Study (SWAN-MPS), by Mia Q. Peng, PhD, MPH, and colleagues, have been published online in the Journal of Clinical Endocrinology & Metabolism.

“Overall, our study has added some evidence to support the potential diabetogenic effects of phthalates, but it also highlights that much is still unknown about the metabolic effects of these chemicals,” the group noted.

“The apparent racial/ethnic differences in the associations between phthalates and incident diabetes should be investigated in future studies,” they cautioned.

Recruiting younger participants and observing them longer, they suggested, “will also help us understand the effects of phthalates on different stages of the diabetogenic process, including whether body fat gain is an important mediator.”
 

Phthalates are all around us

Low-molecular-weight phthalates are frequently added to personal care products, such as fragrance, nail polish, and some feminine hygiene products, as solvents, plasticizers, and fixatives, the researchers explained.

And high-molecular-weight phthalates are frequently added to polyvinyl chloride plastic products, such as plastic food packaging, clothing, and vinyl flooring, as plasticizers.

Phthalates have been hypothesized to contribute to the development of diabetes, but longitudinal evidence in humans was limited.

“Given widespread exposure to phthalates and the enormous costs of diabetes to individuals and societies, ongoing investments in the research on phthalates’ metabolic effects are warranted,” the researchers concluded.
 

Racial differences in phthalates and incident diabetes

“A new finding is that we observed some phthalates are associated with a higher risk of diabetes development, especially in White women [that] were not seen in Black or Asian women,” senior author Sung Kyun Park, ScD, MPH, of the University of Michigan, Ann Arbor, told this news organization.

“We were surprised to see the racial/ethnic differences,” added Dr. Peng, formerly of the University of Michigan and now at Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus.

A possible explanation is that “compared to White women, Black women develop diabetes at a younger age and are exposed to higher levels of several phthalates,” and this study excluded women who already had diabetes by midlife, she noted.

“Although our study was conducted in a cohort of women,” Dr. Park stressed, “we hope that our findings are not interpreted that only women should be concerned of phthalates. Our findings add to the current literature that phthalates may be a potential risk factor for type 2 diabetes.

“Certain phthalates are prohibited in children’s toys and child care articles,” Dr. Peng noted, as explained by the U.S. Consumer Product Safety Commission. In addition, a bill has been introduced in Congress to ban phthalates in food contact substances.

“If phthalates are removed from plastics and other consumer products,” she cautioned, “we do have to be careful in the process to avoid replacing them with some other potentially harmful chemicals.”

A well-known example of this type of “regrettable substitution,” Dr. Park added, “is ‘BPA-free’ plastics that replaced bisphenol A with other bisphenols such as bisphenol-F (BPF) or bisphenol-S (BPS). The product has a label of ‘BPA-free’, but those replaced chemicals turned out to be equally toxic. Science is slow to determine if a new chemical introduced to the market is safe and can replace a regulated chemical.”

And studies have shown that a diet rich in meat, fat, and ultraprocessed foods is associated with increased exposures to some phthalates, especially when the foods are obtained away from home, such as fast foods, Dr. Peng observed. In addition, some phthalates are added to personal care products such as fragrance.

“As a first step,” she said, “I think reducing consumption of ultraprocessed foods packaged in plastics may help reduce phthalate exposure.”

A 2020 report from the Endocrine Society and the International Pollutants Elimination Network (IPEN), titled, “Plastics, EDCs, and Health,” summarizes research on bisphenol A, per- and polyfluoroalkyl substances (PFAS), phthalates, and other EDCs that leach from plastics. The Endocrine Society website also has a link to a 2-page summary.  
 

Levels of 12 phthalate metabolites

Previously, the researchers reported how another class of “forever chemicals,” PFAS, were associated with risk of hypertension in a 17-year follow-up of middle-aged women in the SWAN study.

In the current study, they analyzed data from 1,308 women in SWAN-MPS who had been recruited at five study sites (Oakland, Calif; Los Angeles; Detroit; Pittsburgh; and Boston).

The women were between ages 42 and 52 years in 1996-1997 and self-identified as White, Black, Chinese, or Japanese.

They did not have diabetes in 1999-2000 and had sufficient urine samples for phthalate assessment then and midway through a 6-year follow-up.

The women were a median age of 49 years in 1999-2000. About half were White, 20% were Black, 13% were Chinese, and 15% were Japanese.

Researchers analyzed levels of 12 metabolites, chosen because their parent phthalates have been widely used in industry and commerce, and exposure to these phthalates is a national biomonitoring priority.

The measured phthalates were:

Three metabolites of low-molecular-weight phthalates:

• mono-ethyl phthalate (MEP)
• mono-n-butyl phthalate (MnBP)
• mono-isobutyl phthalate (MiBP)

Four metabolites of the high-molecular-weight phthalate di(2-ethylhexyl) phthalate (DEHP), which is of particular public health interest:

• mono(2-ethylhexyl) phthalate (MEHP)
• mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)
• mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)
• mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)

Five metabolites of other high-molecular-weight phthalates:

• monobenzyl phthalate (MBzP)
• monoisononyl phthalate (MiNP)
• mono-carboxyoctyl phthalate (MCOP)
• mono-carboxy-isononyl phthalate (MCNP)
• mono(3-carboxypropyl) phthalate (MCPP)

The researchers excluded MiNP from all analyses because it was detected in less than 1% of urine samples.

The different phthalate metabolites were detected in 84.8% of samples (MEHP) to 100% of samples (MnBP and MECPP).

Women who were younger, Black, current smokers, or obese generally had higher concentrations of phthalate metabolites.

Over 6 years, 61 women developed diabetes (an incidence rate of 8.1 per 1000 person-years).

Compared with other women, those with incident diabetes had significantly higher concentrations of all phthalate metabolites except DEHP metabolites and MCPP. 

Phthalates were not associated with incident diabetes in Black or Asian women.

However, among White women, each doubling of the concentrations of MiBP, MBzP, MCOP, MCNP, and MCCP was associated with a 30% to 63% higher incidence of diabetes (HR 1.30 for MCNP; HR 1.63 for MiBP).

The SWAN study was supported by the National Institutes of Health, Department of Health & Human Services, National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and SWAN Repository. The current study was supported by the National Center for Research Resources, National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. Dr. Peng was supported by an Interdisciplinary Research Training on Health and Aging grant from the NIA. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

HMG-CoA reductase inhibitors (statins) have been shown to effectively reduce low-density lipoprotein cholesterol (LDL-C) as well as morbidity and mortality in patients who have either atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD.^1-12 However, research shows that up to 20% of patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs).¹³ This presents a substantial clinical challenge, as current management strategies for patients with statin-associated muscle symptoms, such as intermittent administration of statins and ezetimibe, seldom achieve the > 50% LDL-C reduction recommended by the 2018 American Heart Association/American College of Cardiology Clinical Practice Guidelines.¹⁴ Additionally, statin-intolerant patients who have antihyperlipidemic medication lowered or discontinued are at an increased risk of future cardiovascular events.¹⁵ Observational data also show that about 70% of adult patients (primarily with genetic lipid disorders such as heterozygous familial hypercholesterolemia) do not achieve an LDL-C level < 100 mg/dL despite treatment with maximum doses of statins with or without ezetimibe.^16,17

PCSK9 inhibitors (PCSK9i) have robust efficacy data to support use in patients who do not meet their LDL-C goal despite maximally tolerated lipid therapy.¹⁴ However, long-term safety data for PCSK9i are not as robust as its efficacy data. Specifically, safety data relating to muscle-related AEs, which are the most widely recognized AE associated with statins, have only been reported in a few clinical trials with varying incidence rates, levels of significance, and relatively small study populations. Furthermore, the real-world prevalence of muscle-related PCSK9i AEs is unknown. Clinical guidance for management strategies for muscle-related AEs associated with PCSK9i is largely lacking. For this study, muscle-related AEs were defined as any new or unusual muscle soreness, weakness, cramping, aches, and stiffness that persists, is generally bilateral, and typically affects the large muscles. It is important to note, that muscle-related AEs associated with statins, ezetimibe, and PCSK9i can be attributed to the nocebo effect.

According to the prescribing information for alirocumab and evolocumab, myalgia, muscle spasms, and musculoskeletal pain each occurred in < 5% of the study populations.^18,19 From these data, muscle-related PCSK9i AEs are thought to be relatively rare, based on the ODYSSEY-OUTCOME and FOURIER trials, which did not enroll statin-intolerant patients.^20,21 However, currently available safety data from 3 small, randomized clinical trials specifically in statin-intolerant patients taking a PCSK9i suggest that muscle-related AEs occur at a rate of 12.2% to 32.5% and discontinuation rates varied from 0% to 15.9%.^22-25 As the incidence rates of muscle-related AEs in the prescribing information and clinical trials varied widely, this study will provide quantitative data on the percentage of patients that developed muscle-related PCSK9i AEs in a veteran population to help shed light on a topic that is not well studied.

Methods

This was a single-center, retrospective chart review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, and were managed in a pharmacy-led patient aligned care team (PACT) clinic at the Wilkes-Barre US Department of Veterans Affairs (VA) Medical Center (WBVAMC) in Pennsylvania. This study was approved by the Coatesville VA Medical Center Institutional Review Board, which oversees research conducted at WBVAMC. Veterans aged ≥ 18 years were included in the study. Patients were excluded if they had a history of serious hypersensitivity reaction to a PCSK9i or rhabdomyolysis or did not meet the VA criteria for use.²⁶

The primary outcome was the percentage of patients who developed a muscle-related AE while on a PCSK9i in a PACT clinic. Data were further analyzed based on patients who (1) tolerated a full PCSK9i dose; (2) tolerated alternative PCSK9i following initial intolerance; (3) required a PCSK9i dose reduction, or (4) discontinued PCSK9i. A secondary outcome was the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their LDL-C goal. Management strategies that were assessed included restarting weekly statin, restarting weekly ezetimibe, increasing the dose of the same PCSK9i administered monthly, and switching to an alternative PCSK9i.

Data were collected using the VA Computerized Patient Record System (CPRS) and stored in a secure, locked spreadsheet. Baseline patient demographic characteristics collected included age (at PCSK9i start); sex; race; and PCSK9i name, dose, and frequency. We recorded when a patient switched PCSK9i, whether or not it was due to a muscle-related AE, and the name of the original PCSK9i. Also collected were lipid therapy intolerances prior to PCSK9i initiation (ie, intolerance to statin, ezetimibe, or both).

Patients were considered statin intolerant due to a muscle-related AE in accordance with the VA PCSK9i Criteria for Use, which requires trial of at least 3 statins, one of which was trialed at the lowest dosage approved by the US Food and Drug Administration (FDA) and resulted in intolerable skeletal muscle AEs that worsened during treatment and resolved when the statin was stopped. For our study purposes, patients taking alternative day dosing of statins due to muscle-related AEs (ie, 2- or 3-times weekly dosing) were not considered statin intolerant; however, patients taking once-weekly statin dosing were considered statin intolerant. Patients were considered ezetimibe intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when ezetimibe was stopped. Patients were considered PCSK9i intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when the PCSK9i was stopped. Patients with non–muscle-related intolerances to statins, ezetimibe, and PCSK9i were not considered statin, ezetimibe, and PCSK9i intolerant.

Alirocumab was initiated at 75 mg subcutaneous (SQ) once every 2 weeks or evolocumab 140 mg SQ once every 2 weeks in our study. The protocol allowed for a dose reduction of alirocumab 75 mg SQ once monthly if a patient experienced AEs, but this dose reduction strategy was not used for any patients on evolocumab in this study. Of note, alirocumab 75 mg SQ once monthly is not an FDA-approved dosing strategy. However, it is similar in concept to the alternative statin dosing (ie, alternate day dosing, once-weekly dosing) and may avoid the need to discontinue PCSK9i therapy altogether.

A review of the CPRS also documented whether a muscle-related AE occurred while the patient was on a PCSK9i (if yes, the specific AE was recorded), the result of PCSK9i therapy (tolerated full dose, required a dose reduction, switched medication, or discontinued), and management strategies taken for patients who did not meet their LDL-C goal while on a reduced (monthly) PCSK9i dose. Prior lipid therapy intolerances, PCSK9i-related AEs, results of PCSK9i therapy, and management strategies for patients who did not meet LDL-C goal while on a reduced PCSK9i dose were obtained by reviewing the PACT pharmacist’s clinic notes and assessment, along with clinic notes and medication history listed within the CPRS.

Statistical Analysis

Descriptive statistics were used for the demographic characteristics of study patients. The primary outcome was calculated as a binary measure (yes/no) of whether the patient developed a muscle-related AE while on a PCSK9i. The secondary outcome of statin, ezetimibe, or statin and ezetimibe intolerances in subgroups also was calculated as a binary measure.

Results

For the study, 156 charts were reviewed and 137 patients were included (Figure).

For the secondary results, 4 patients (2.9%) tolerated an alternate PCSK9i (evolocumab 140 mg SQ every 2 weeks) after initial intolerance to PCSK9i, 16 (11.7%) required a dose reduction, and 6 (4.4%) discontinued PCSK9i due to a muscle-related AE.

Discussion

This retrospective study found 17.5% of patients experienced muscle-related PCSK9i AEs. These occurred at a higher rate than reported in the prescribing information (< 5%) and were similar to the incidence rates reported in the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE clinical trials (12.0%-32.5%), which is what we hypothesized.^18,19,22-25 It is important to note that the incidence rates of muscle-related AEs reported in the prescribing information for alirocumab and evolocumab were based on trials that did not include statin- and/or ezetimibe-intolerant patients; whereas many patients in our study and patients in the clinical trials were statin and/or ezetimibe intolerant.

Additionally, a new study by Donald and colleagues found an incidence rate of 32% to 36% for muscle-related PCSK9i AEs.²⁷ Collectively, the data from clinical trials and our study indicate that patients with prior intolerances to statin and/or ezetimibe appear to have a higher likelihood of developing a muscle-related PCSK9i intolerance. In our study, 23 of 24 patients who developed a muscle-related PCSK9i AE had a prior history of statin and/or ezetimibe intolerances. This should alert clinicians prescribing PCSK9i in patients with a history of statin and/or ezetimibe intolerance to counsel their patients on the possibility of muscle-related PCSK9i AEs and management strategies. However, it is important to note that there was a substantial number of patients in our study who were statin and/or ezetimibe intolerant due to a prior muscle-related AE who tolerated the full dose of PCSK9i.

To our knowledge, this was the first trial to evaluate muscle-related PCSK9i AEs in a veteran population. Additionally, our study appears to be the first to use 2 PCSK9i dosing strategies that are not FDA approved: Dose reduction for patients who experienced a muscle-related AE on alirocumab 75 mg SQ every 2 weeks and dose escalation for patients who did not meet their LDL-C goal on alirocumab 75 mg SQ monthly following an initial intolerance to 2-week dosing. The dose-reduction strategy allowed patients who experienced a muscle-related AE to alirocumab 75 mg to reduce administration from every 2 weeks to monthly.

This strategy was only performed with alirocumab, the preferred PCSK9i at WBVAMC, but the same dose-reduction strategy can theoretically be used with evolocumab as well. Reduced monthly dosing of alirocumab allowed patients with a prior intolerance to remain on a lower dosage without discontinuation. This is important because as noted by Myers and colleagues, individuals without access to PCSK9i were found to have a significantly higher incidence ratio of cardiovascular events compared with those taking PCSK9i.¹⁵ Also of note, > 30% of patients on the reduced monthly dose of alirocumab still met their LDL-C goal. Therefore, using this dose-reduction strategy (instead of patients discontinuing therapy altogether due to a muscle-related intolerance) can lessen the risk of major adverse cardiovascular events (MACE) as well as mitigate muscle-related AEs that occurred while on 2-week PCSK9i dosing regimens. While we acknowledge that this reduced monthly dose of either alirocumab or evolocumab is not FDA approved, it is similar to alternative statin dosing that also is not FDA approved but may minimize the need to discontinue PCSK9i therapy. It would be beneficial if these dosing strategies were investigated by future research.

The dose-escalation strategy for patients who did not meet their LDL-C goal while on the reduced, monthly dose of alirocumab also was unique. Alirocumab was increased from 75 mg SQ once monthly to 150 mg SQ once monthly. Interestingly, we found that through the end of the chart review period, all patients tolerated the increase well, despite having an initial muscle-related AE to alirocumab 75 mg every 2 weeks, which is the same total monthly dosage. This approach is similar to that of once-weekly statin dosing or a drug holiday and may be explained by the long half-life of PCSK9i. Regardless of the mechanism, this finding suggests that an increased monthly dose of PCSK9i is a potential alternative for patients who cannot tolerate the FDA-approved dose. However, the ability for patients to achieve goal LDL-C on the monthly dosage requires future study.

Limitations

The results of this study should be considered with the following limitations. First, this was a retrospective chart review performed over a prespecified period. Any muscle-related AEs or LDL-C lowering effects from PCSK9i that occurred outside the review period were not captured. Our study was small and only included 137 patients, though it was similar in size to the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE trials.^22-24 Additionally, the study was primarily composed of White men and may not be representative of other populations. Some muscle-related PCSK9i AEs may be attributed to the nocebo. Last, our study did not capture patients on a PCSK9i who were not followed in the PACT clinic.

Conclusions

We found that muscle-related PCSK9i AEs occurred at a similar rate as those reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe had a higher likelihood of developing a muscle-related PCSK9i AE. In our study, only 1 patient developed a muscle-related PCSK9i AE who did not have a prior history of muscle-related intolerance to either a statin or ezetimibe. However, in our study, a substantial percentage of patients with statin and/or ezetimibe intolerances tolerated the full PCSK9i dose well, proving that PCSK9i are still a reasonable alternative for patients with prior intolerances to statins and/or ezetimibe.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the US Department of Veterans Affairs Medical Center, Wilkes-Barre, Pennsylvania.

HMG-CoA reductase inhibitors (statins) have been shown to effectively reduce low-density lipoprotein cholesterol (LDL-C) as well as morbidity and mortality in patients who have either atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD.^1-12 However, research shows that up to 20% of patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs).¹³ This presents a substantial clinical challenge, as current management strategies for patients with statin-associated muscle symptoms, such as intermittent administration of statins and ezetimibe, seldom achieve the > 50% LDL-C reduction recommended by the 2018 American Heart Association/American College of Cardiology Clinical Practice Guidelines.¹⁴ Additionally, statin-intolerant patients who have antihyperlipidemic medication lowered or discontinued are at an increased risk of future cardiovascular events.¹⁵ Observational data also show that about 70% of adult patients (primarily with genetic lipid disorders such as heterozygous familial hypercholesterolemia) do not achieve an LDL-C level < 100 mg/dL despite treatment with maximum doses of statins with or without ezetimibe.^16,17

PCSK9 inhibitors (PCSK9i) have robust efficacy data to support use in patients who do not meet their LDL-C goal despite maximally tolerated lipid therapy.¹⁴ However, long-term safety data for PCSK9i are not as robust as its efficacy data. Specifically, safety data relating to muscle-related AEs, which are the most widely recognized AE associated with statins, have only been reported in a few clinical trials with varying incidence rates, levels of significance, and relatively small study populations. Furthermore, the real-world prevalence of muscle-related PCSK9i AEs is unknown. Clinical guidance for management strategies for muscle-related AEs associated with PCSK9i is largely lacking. For this study, muscle-related AEs were defined as any new or unusual muscle soreness, weakness, cramping, aches, and stiffness that persists, is generally bilateral, and typically affects the large muscles. It is important to note, that muscle-related AEs associated with statins, ezetimibe, and PCSK9i can be attributed to the nocebo effect.

According to the prescribing information for alirocumab and evolocumab, myalgia, muscle spasms, and musculoskeletal pain each occurred in < 5% of the study populations.^18,19 From these data, muscle-related PCSK9i AEs are thought to be relatively rare, based on the ODYSSEY-OUTCOME and FOURIER trials, which did not enroll statin-intolerant patients.^20,21 However, currently available safety data from 3 small, randomized clinical trials specifically in statin-intolerant patients taking a PCSK9i suggest that muscle-related AEs occur at a rate of 12.2% to 32.5% and discontinuation rates varied from 0% to 15.9%.^22-25 As the incidence rates of muscle-related AEs in the prescribing information and clinical trials varied widely, this study will provide quantitative data on the percentage of patients that developed muscle-related PCSK9i AEs in a veteran population to help shed light on a topic that is not well studied.

Methods

This was a single-center, retrospective chart review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, and were managed in a pharmacy-led patient aligned care team (PACT) clinic at the Wilkes-Barre US Department of Veterans Affairs (VA) Medical Center (WBVAMC) in Pennsylvania. This study was approved by the Coatesville VA Medical Center Institutional Review Board, which oversees research conducted at WBVAMC. Veterans aged ≥ 18 years were included in the study. Patients were excluded if they had a history of serious hypersensitivity reaction to a PCSK9i or rhabdomyolysis or did not meet the VA criteria for use.²⁶

The primary outcome was the percentage of patients who developed a muscle-related AE while on a PCSK9i in a PACT clinic. Data were further analyzed based on patients who (1) tolerated a full PCSK9i dose; (2) tolerated alternative PCSK9i following initial intolerance; (3) required a PCSK9i dose reduction, or (4) discontinued PCSK9i. A secondary outcome was the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their LDL-C goal. Management strategies that were assessed included restarting weekly statin, restarting weekly ezetimibe, increasing the dose of the same PCSK9i administered monthly, and switching to an alternative PCSK9i.

Data were collected using the VA Computerized Patient Record System (CPRS) and stored in a secure, locked spreadsheet. Baseline patient demographic characteristics collected included age (at PCSK9i start); sex; race; and PCSK9i name, dose, and frequency. We recorded when a patient switched PCSK9i, whether or not it was due to a muscle-related AE, and the name of the original PCSK9i. Also collected were lipid therapy intolerances prior to PCSK9i initiation (ie, intolerance to statin, ezetimibe, or both).

Patients were considered statin intolerant due to a muscle-related AE in accordance with the VA PCSK9i Criteria for Use, which requires trial of at least 3 statins, one of which was trialed at the lowest dosage approved by the US Food and Drug Administration (FDA) and resulted in intolerable skeletal muscle AEs that worsened during treatment and resolved when the statin was stopped. For our study purposes, patients taking alternative day dosing of statins due to muscle-related AEs (ie, 2- or 3-times weekly dosing) were not considered statin intolerant; however, patients taking once-weekly statin dosing were considered statin intolerant. Patients were considered ezetimibe intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when ezetimibe was stopped. Patients were considered PCSK9i intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when the PCSK9i was stopped. Patients with non–muscle-related intolerances to statins, ezetimibe, and PCSK9i were not considered statin, ezetimibe, and PCSK9i intolerant.

Alirocumab was initiated at 75 mg subcutaneous (SQ) once every 2 weeks or evolocumab 140 mg SQ once every 2 weeks in our study. The protocol allowed for a dose reduction of alirocumab 75 mg SQ once monthly if a patient experienced AEs, but this dose reduction strategy was not used for any patients on evolocumab in this study. Of note, alirocumab 75 mg SQ once monthly is not an FDA-approved dosing strategy. However, it is similar in concept to the alternative statin dosing (ie, alternate day dosing, once-weekly dosing) and may avoid the need to discontinue PCSK9i therapy altogether.

A review of the CPRS also documented whether a muscle-related AE occurred while the patient was on a PCSK9i (if yes, the specific AE was recorded), the result of PCSK9i therapy (tolerated full dose, required a dose reduction, switched medication, or discontinued), and management strategies taken for patients who did not meet their LDL-C goal while on a reduced (monthly) PCSK9i dose. Prior lipid therapy intolerances, PCSK9i-related AEs, results of PCSK9i therapy, and management strategies for patients who did not meet LDL-C goal while on a reduced PCSK9i dose were obtained by reviewing the PACT pharmacist’s clinic notes and assessment, along with clinic notes and medication history listed within the CPRS.

Statistical Analysis

Descriptive statistics were used for the demographic characteristics of study patients. The primary outcome was calculated as a binary measure (yes/no) of whether the patient developed a muscle-related AE while on a PCSK9i. The secondary outcome of statin, ezetimibe, or statin and ezetimibe intolerances in subgroups also was calculated as a binary measure.

Results

For the study, 156 charts were reviewed and 137 patients were included (Figure).

For the secondary results, 4 patients (2.9%) tolerated an alternate PCSK9i (evolocumab 140 mg SQ every 2 weeks) after initial intolerance to PCSK9i, 16 (11.7%) required a dose reduction, and 6 (4.4%) discontinued PCSK9i due to a muscle-related AE.

Discussion

This retrospective study found 17.5% of patients experienced muscle-related PCSK9i AEs. These occurred at a higher rate than reported in the prescribing information (< 5%) and were similar to the incidence rates reported in the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE clinical trials (12.0%-32.5%), which is what we hypothesized.^18,19,22-25 It is important to note that the incidence rates of muscle-related AEs reported in the prescribing information for alirocumab and evolocumab were based on trials that did not include statin- and/or ezetimibe-intolerant patients; whereas many patients in our study and patients in the clinical trials were statin and/or ezetimibe intolerant.

Additionally, a new study by Donald and colleagues found an incidence rate of 32% to 36% for muscle-related PCSK9i AEs.²⁷ Collectively, the data from clinical trials and our study indicate that patients with prior intolerances to statin and/or ezetimibe appear to have a higher likelihood of developing a muscle-related PCSK9i intolerance. In our study, 23 of 24 patients who developed a muscle-related PCSK9i AE had a prior history of statin and/or ezetimibe intolerances. This should alert clinicians prescribing PCSK9i in patients with a history of statin and/or ezetimibe intolerance to counsel their patients on the possibility of muscle-related PCSK9i AEs and management strategies. However, it is important to note that there was a substantial number of patients in our study who were statin and/or ezetimibe intolerant due to a prior muscle-related AE who tolerated the full dose of PCSK9i.

To our knowledge, this was the first trial to evaluate muscle-related PCSK9i AEs in a veteran population. Additionally, our study appears to be the first to use 2 PCSK9i dosing strategies that are not FDA approved: Dose reduction for patients who experienced a muscle-related AE on alirocumab 75 mg SQ every 2 weeks and dose escalation for patients who did not meet their LDL-C goal on alirocumab 75 mg SQ monthly following an initial intolerance to 2-week dosing. The dose-reduction strategy allowed patients who experienced a muscle-related AE to alirocumab 75 mg to reduce administration from every 2 weeks to monthly.

This strategy was only performed with alirocumab, the preferred PCSK9i at WBVAMC, but the same dose-reduction strategy can theoretically be used with evolocumab as well. Reduced monthly dosing of alirocumab allowed patients with a prior intolerance to remain on a lower dosage without discontinuation. This is important because as noted by Myers and colleagues, individuals without access to PCSK9i were found to have a significantly higher incidence ratio of cardiovascular events compared with those taking PCSK9i.¹⁵ Also of note, > 30% of patients on the reduced monthly dose of alirocumab still met their LDL-C goal. Therefore, using this dose-reduction strategy (instead of patients discontinuing therapy altogether due to a muscle-related intolerance) can lessen the risk of major adverse cardiovascular events (MACE) as well as mitigate muscle-related AEs that occurred while on 2-week PCSK9i dosing regimens. While we acknowledge that this reduced monthly dose of either alirocumab or evolocumab is not FDA approved, it is similar to alternative statin dosing that also is not FDA approved but may minimize the need to discontinue PCSK9i therapy. It would be beneficial if these dosing strategies were investigated by future research.

The dose-escalation strategy for patients who did not meet their LDL-C goal while on the reduced, monthly dose of alirocumab also was unique. Alirocumab was increased from 75 mg SQ once monthly to 150 mg SQ once monthly. Interestingly, we found that through the end of the chart review period, all patients tolerated the increase well, despite having an initial muscle-related AE to alirocumab 75 mg every 2 weeks, which is the same total monthly dosage. This approach is similar to that of once-weekly statin dosing or a drug holiday and may be explained by the long half-life of PCSK9i. Regardless of the mechanism, this finding suggests that an increased monthly dose of PCSK9i is a potential alternative for patients who cannot tolerate the FDA-approved dose. However, the ability for patients to achieve goal LDL-C on the monthly dosage requires future study.

Limitations

The results of this study should be considered with the following limitations. First, this was a retrospective chart review performed over a prespecified period. Any muscle-related AEs or LDL-C lowering effects from PCSK9i that occurred outside the review period were not captured. Our study was small and only included 137 patients, though it was similar in size to the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE trials.^22-24 Additionally, the study was primarily composed of White men and may not be representative of other populations. Some muscle-related PCSK9i AEs may be attributed to the nocebo. Last, our study did not capture patients on a PCSK9i who were not followed in the PACT clinic.

Conclusions

We found that muscle-related PCSK9i AEs occurred at a similar rate as those reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe had a higher likelihood of developing a muscle-related PCSK9i AE. In our study, only 1 patient developed a muscle-related PCSK9i AE who did not have a prior history of muscle-related intolerance to either a statin or ezetimibe. However, in our study, a substantial percentage of patients with statin and/or ezetimibe intolerances tolerated the full PCSK9i dose well, proving that PCSK9i are still a reasonable alternative for patients with prior intolerances to statins and/or ezetimibe.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the US Department of Veterans Affairs Medical Center, Wilkes-Barre, Pennsylvania.

HMG-CoA reductase inhibitors (statins) have been shown to effectively reduce low-density lipoprotein cholesterol (LDL-C) as well as morbidity and mortality in patients who have either atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD.^1-12 However, research shows that up to 20% of patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs).¹³ This presents a substantial clinical challenge, as current management strategies for patients with statin-associated muscle symptoms, such as intermittent administration of statins and ezetimibe, seldom achieve the > 50% LDL-C reduction recommended by the 2018 American Heart Association/American College of Cardiology Clinical Practice Guidelines.¹⁴ Additionally, statin-intolerant patients who have antihyperlipidemic medication lowered or discontinued are at an increased risk of future cardiovascular events.¹⁵ Observational data also show that about 70% of adult patients (primarily with genetic lipid disorders such as heterozygous familial hypercholesterolemia) do not achieve an LDL-C level < 100 mg/dL despite treatment with maximum doses of statins with or without ezetimibe.^16,17

PCSK9 inhibitors (PCSK9i) have robust efficacy data to support use in patients who do not meet their LDL-C goal despite maximally tolerated lipid therapy.¹⁴ However, long-term safety data for PCSK9i are not as robust as its efficacy data. Specifically, safety data relating to muscle-related AEs, which are the most widely recognized AE associated with statins, have only been reported in a few clinical trials with varying incidence rates, levels of significance, and relatively small study populations. Furthermore, the real-world prevalence of muscle-related PCSK9i AEs is unknown. Clinical guidance for management strategies for muscle-related AEs associated with PCSK9i is largely lacking. For this study, muscle-related AEs were defined as any new or unusual muscle soreness, weakness, cramping, aches, and stiffness that persists, is generally bilateral, and typically affects the large muscles. It is important to note, that muscle-related AEs associated with statins, ezetimibe, and PCSK9i can be attributed to the nocebo effect.

According to the prescribing information for alirocumab and evolocumab, myalgia, muscle spasms, and musculoskeletal pain each occurred in < 5% of the study populations.^18,19 From these data, muscle-related PCSK9i AEs are thought to be relatively rare, based on the ODYSSEY-OUTCOME and FOURIER trials, which did not enroll statin-intolerant patients.^20,21 However, currently available safety data from 3 small, randomized clinical trials specifically in statin-intolerant patients taking a PCSK9i suggest that muscle-related AEs occur at a rate of 12.2% to 32.5% and discontinuation rates varied from 0% to 15.9%.^22-25 As the incidence rates of muscle-related AEs in the prescribing information and clinical trials varied widely, this study will provide quantitative data on the percentage of patients that developed muscle-related PCSK9i AEs in a veteran population to help shed light on a topic that is not well studied.

Methods

This was a single-center, retrospective chart review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, and were managed in a pharmacy-led patient aligned care team (PACT) clinic at the Wilkes-Barre US Department of Veterans Affairs (VA) Medical Center (WBVAMC) in Pennsylvania. This study was approved by the Coatesville VA Medical Center Institutional Review Board, which oversees research conducted at WBVAMC. Veterans aged ≥ 18 years were included in the study. Patients were excluded if they had a history of serious hypersensitivity reaction to a PCSK9i or rhabdomyolysis or did not meet the VA criteria for use.²⁶

The primary outcome was the percentage of patients who developed a muscle-related AE while on a PCSK9i in a PACT clinic. Data were further analyzed based on patients who (1) tolerated a full PCSK9i dose; (2) tolerated alternative PCSK9i following initial intolerance; (3) required a PCSK9i dose reduction, or (4) discontinued PCSK9i. A secondary outcome was the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their LDL-C goal. Management strategies that were assessed included restarting weekly statin, restarting weekly ezetimibe, increasing the dose of the same PCSK9i administered monthly, and switching to an alternative PCSK9i.

Data were collected using the VA Computerized Patient Record System (CPRS) and stored in a secure, locked spreadsheet. Baseline patient demographic characteristics collected included age (at PCSK9i start); sex; race; and PCSK9i name, dose, and frequency. We recorded when a patient switched PCSK9i, whether or not it was due to a muscle-related AE, and the name of the original PCSK9i. Also collected were lipid therapy intolerances prior to PCSK9i initiation (ie, intolerance to statin, ezetimibe, or both).

Patients were considered statin intolerant due to a muscle-related AE in accordance with the VA PCSK9i Criteria for Use, which requires trial of at least 3 statins, one of which was trialed at the lowest dosage approved by the US Food and Drug Administration (FDA) and resulted in intolerable skeletal muscle AEs that worsened during treatment and resolved when the statin was stopped. For our study purposes, patients taking alternative day dosing of statins due to muscle-related AEs (ie, 2- or 3-times weekly dosing) were not considered statin intolerant; however, patients taking once-weekly statin dosing were considered statin intolerant. Patients were considered ezetimibe intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when ezetimibe was stopped. Patients were considered PCSK9i intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when the PCSK9i was stopped. Patients with non–muscle-related intolerances to statins, ezetimibe, and PCSK9i were not considered statin, ezetimibe, and PCSK9i intolerant.

Alirocumab was initiated at 75 mg subcutaneous (SQ) once every 2 weeks or evolocumab 140 mg SQ once every 2 weeks in our study. The protocol allowed for a dose reduction of alirocumab 75 mg SQ once monthly if a patient experienced AEs, but this dose reduction strategy was not used for any patients on evolocumab in this study. Of note, alirocumab 75 mg SQ once monthly is not an FDA-approved dosing strategy. However, it is similar in concept to the alternative statin dosing (ie, alternate day dosing, once-weekly dosing) and may avoid the need to discontinue PCSK9i therapy altogether.

A review of the CPRS also documented whether a muscle-related AE occurred while the patient was on a PCSK9i (if yes, the specific AE was recorded), the result of PCSK9i therapy (tolerated full dose, required a dose reduction, switched medication, or discontinued), and management strategies taken for patients who did not meet their LDL-C goal while on a reduced (monthly) PCSK9i dose. Prior lipid therapy intolerances, PCSK9i-related AEs, results of PCSK9i therapy, and management strategies for patients who did not meet LDL-C goal while on a reduced PCSK9i dose were obtained by reviewing the PACT pharmacist’s clinic notes and assessment, along with clinic notes and medication history listed within the CPRS.

Statistical Analysis

Descriptive statistics were used for the demographic characteristics of study patients. The primary outcome was calculated as a binary measure (yes/no) of whether the patient developed a muscle-related AE while on a PCSK9i. The secondary outcome of statin, ezetimibe, or statin and ezetimibe intolerances in subgroups also was calculated as a binary measure.

Results

For the study, 156 charts were reviewed and 137 patients were included (Figure).

For the secondary results, 4 patients (2.9%) tolerated an alternate PCSK9i (evolocumab 140 mg SQ every 2 weeks) after initial intolerance to PCSK9i, 16 (11.7%) required a dose reduction, and 6 (4.4%) discontinued PCSK9i due to a muscle-related AE.

Discussion

This retrospective study found 17.5% of patients experienced muscle-related PCSK9i AEs. These occurred at a higher rate than reported in the prescribing information (< 5%) and were similar to the incidence rates reported in the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE clinical trials (12.0%-32.5%), which is what we hypothesized.^18,19,22-25 It is important to note that the incidence rates of muscle-related AEs reported in the prescribing information for alirocumab and evolocumab were based on trials that did not include statin- and/or ezetimibe-intolerant patients; whereas many patients in our study and patients in the clinical trials were statin and/or ezetimibe intolerant.

Additionally, a new study by Donald and colleagues found an incidence rate of 32% to 36% for muscle-related PCSK9i AEs.²⁷ Collectively, the data from clinical trials and our study indicate that patients with prior intolerances to statin and/or ezetimibe appear to have a higher likelihood of developing a muscle-related PCSK9i intolerance. In our study, 23 of 24 patients who developed a muscle-related PCSK9i AE had a prior history of statin and/or ezetimibe intolerances. This should alert clinicians prescribing PCSK9i in patients with a history of statin and/or ezetimibe intolerance to counsel their patients on the possibility of muscle-related PCSK9i AEs and management strategies. However, it is important to note that there was a substantial number of patients in our study who were statin and/or ezetimibe intolerant due to a prior muscle-related AE who tolerated the full dose of PCSK9i.

To our knowledge, this was the first trial to evaluate muscle-related PCSK9i AEs in a veteran population. Additionally, our study appears to be the first to use 2 PCSK9i dosing strategies that are not FDA approved: Dose reduction for patients who experienced a muscle-related AE on alirocumab 75 mg SQ every 2 weeks and dose escalation for patients who did not meet their LDL-C goal on alirocumab 75 mg SQ monthly following an initial intolerance to 2-week dosing. The dose-reduction strategy allowed patients who experienced a muscle-related AE to alirocumab 75 mg to reduce administration from every 2 weeks to monthly.

This strategy was only performed with alirocumab, the preferred PCSK9i at WBVAMC, but the same dose-reduction strategy can theoretically be used with evolocumab as well. Reduced monthly dosing of alirocumab allowed patients with a prior intolerance to remain on a lower dosage without discontinuation. This is important because as noted by Myers and colleagues, individuals without access to PCSK9i were found to have a significantly higher incidence ratio of cardiovascular events compared with those taking PCSK9i.¹⁵ Also of note, > 30% of patients on the reduced monthly dose of alirocumab still met their LDL-C goal. Therefore, using this dose-reduction strategy (instead of patients discontinuing therapy altogether due to a muscle-related intolerance) can lessen the risk of major adverse cardiovascular events (MACE) as well as mitigate muscle-related AEs that occurred while on 2-week PCSK9i dosing regimens. While we acknowledge that this reduced monthly dose of either alirocumab or evolocumab is not FDA approved, it is similar to alternative statin dosing that also is not FDA approved but may minimize the need to discontinue PCSK9i therapy. It would be beneficial if these dosing strategies were investigated by future research.

The dose-escalation strategy for patients who did not meet their LDL-C goal while on the reduced, monthly dose of alirocumab also was unique. Alirocumab was increased from 75 mg SQ once monthly to 150 mg SQ once monthly. Interestingly, we found that through the end of the chart review period, all patients tolerated the increase well, despite having an initial muscle-related AE to alirocumab 75 mg every 2 weeks, which is the same total monthly dosage. This approach is similar to that of once-weekly statin dosing or a drug holiday and may be explained by the long half-life of PCSK9i. Regardless of the mechanism, this finding suggests that an increased monthly dose of PCSK9i is a potential alternative for patients who cannot tolerate the FDA-approved dose. However, the ability for patients to achieve goal LDL-C on the monthly dosage requires future study.

Limitations

The results of this study should be considered with the following limitations. First, this was a retrospective chart review performed over a prespecified period. Any muscle-related AEs or LDL-C lowering effects from PCSK9i that occurred outside the review period were not captured. Our study was small and only included 137 patients, though it was similar in size to the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE trials.^22-24 Additionally, the study was primarily composed of White men and may not be representative of other populations. Some muscle-related PCSK9i AEs may be attributed to the nocebo. Last, our study did not capture patients on a PCSK9i who were not followed in the PACT clinic.

Conclusions

We found that muscle-related PCSK9i AEs occurred at a similar rate as those reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe had a higher likelihood of developing a muscle-related PCSK9i AE. In our study, only 1 patient developed a muscle-related PCSK9i AE who did not have a prior history of muscle-related intolerance to either a statin or ezetimibe. However, in our study, a substantial percentage of patients with statin and/or ezetimibe intolerances tolerated the full PCSK9i dose well, proving that PCSK9i are still a reasonable alternative for patients with prior intolerances to statins and/or ezetimibe.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the US Department of Veterans Affairs Medical Center, Wilkes-Barre, Pennsylvania.

The European Commission has expanded the indication for dapagliflozin (Forxiga) to include heart failure across the full spectrum of left ventricular ejection fraction – including HF with mildly reduced and preserved ejection fraction, AstraZeneca has announced.

The EC nod for the sodium-glucose cotransporter 2 (SGLT2) inhibitor (known as Farxiga in the United States) follows the positive opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency in December 2022.

The committee’s decision was based on results from the DELIVER phase 3 trial, which showed clear clinical benefits of the SGLT2 inhibitor in patients with HF regardless of their left ventricular function.

The study was published in the New England Journal of Medicine and presented at the European Society of Cardiology’s annual congress.

The data support the use of SGLT2 inhibitors as “foundational agents for virtually all patients with heart failure” regardless of their ejection fraction or whether or not they have type 2 diabetes, said study presenter Scott D. Solomon, MD, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston.

The Food and Drug Administration is currently reviewing AstraZeneca’s application to expand the HF indication for dapagliflozin in the United States.

A version of this article first appeared on Medscape.com.

The European Commission has expanded the indication for dapagliflozin (Forxiga) to include heart failure across the full spectrum of left ventricular ejection fraction – including HF with mildly reduced and preserved ejection fraction, AstraZeneca has announced.

The EC nod for the sodium-glucose cotransporter 2 (SGLT2) inhibitor (known as Farxiga in the United States) follows the positive opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency in December 2022.

The committee’s decision was based on results from the DELIVER phase 3 trial, which showed clear clinical benefits of the SGLT2 inhibitor in patients with HF regardless of their left ventricular function.

The study was published in the New England Journal of Medicine and presented at the European Society of Cardiology’s annual congress.

The data support the use of SGLT2 inhibitors as “foundational agents for virtually all patients with heart failure” regardless of their ejection fraction or whether or not they have type 2 diabetes, said study presenter Scott D. Solomon, MD, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston.

The Food and Drug Administration is currently reviewing AstraZeneca’s application to expand the HF indication for dapagliflozin in the United States.

A version of this article first appeared on Medscape.com.

The European Commission has expanded the indication for dapagliflozin (Forxiga) to include heart failure across the full spectrum of left ventricular ejection fraction – including HF with mildly reduced and preserved ejection fraction, AstraZeneca has announced.

The EC nod for the sodium-glucose cotransporter 2 (SGLT2) inhibitor (known as Farxiga in the United States) follows the positive opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency in December 2022.

The committee’s decision was based on results from the DELIVER phase 3 trial, which showed clear clinical benefits of the SGLT2 inhibitor in patients with HF regardless of their left ventricular function.

The study was published in the New England Journal of Medicine and presented at the European Society of Cardiology’s annual congress.

The data support the use of SGLT2 inhibitors as “foundational agents for virtually all patients with heart failure” regardless of their ejection fraction or whether or not they have type 2 diabetes, said study presenter Scott D. Solomon, MD, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston.

The Food and Drug Administration is currently reviewing AstraZeneca’s application to expand the HF indication for dapagliflozin in the United States.

A version of this article first appeared on Medscape.com.