Diabetes

Automotive-themed workshops that refer to doctor visits as “tune-ups” and nutritious food as “high-performance fuel” are showing promise as a strategy to better explain diabetes self-management to Mexican American men, an investigator has reported.

Ronnie Kaufman/DigitalVision

The workshops, which started out in person and transitioned online because of the COVID-19 pandemic, have improved self-care behaviors among Mexican American men with diabetes, said Jeannie Belinda Concha, PhD, MPH, of the University of Texas, El Paso.

After participating in the workshops, known as The Diabetes Garage, men more often measured food portions and counted carbohydrates, and had improved confidence in their ability to self-manage their diabetes, Dr. Concha said in a virtual presentation on the study.

Although those improvements in self-care behaviors didn’t translate into significant improvements in blood pressure or hemoglobin A1c, she said, they could be predecessors to improved physical health outcomes with longer follow-up.

”We know it takes some time to move those numbers, but they are going in the right direction,” Dr. Concha said in her presentation, which took place during the annual scientific sessions of the American Diabetes Association.
 

Meeting Mexican American men where they’re at

Robert Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said The Diabetes Garage is an “innovative” approach to tailoring diabetes self-care message for a specific of individuals.

“It’s such a wonderful example of something that we believe so strongly, which is that you’ve got to meet people where they’re at,” Dr. Gabbay said in an interview.

“We know that people learn in different ways, and people and with different backgrounds have different things that resonate with them,” he continued. “For better or worse, one size doesn’t fit all, and that in a sense is one of the challenges around diabetes, because we’re really trying to help everybody.”
 

Unmet needs for diabetes education

The prevalence of diabetes in the United States is high among Hispanics, higher among Mexican Americans, and even higher still among Mexican-American men, according to Dr. Concha.

The age-adjusted prevalence of diabetes is 16.2% among Mexican-American men, as compared with 12.8% for Mexican American women, and 8.6% for White non-Hispanic men, according to 2018 data from the Centers for Disease Control and Prevention that Dr. Concha highlighted in her presentation.

Moreover, only 25% of participants in diabetes education are men, highlighting another disparity that needs to be addressed, she said.
 

Infusing diabetes self-management with car culture

The Diabetes Garage leverages a positive “car culture” that is prevalent in Mexican American communities in general, and cities like El Paso in particular, Dr. Concha said.

This culture brings Mexican American people together at numerous car shows, and is viewed as a form of family identification for enthusiasts, who will illustrate their own pride by customizing their cars with cultural symbols, according to Dr. Concha.

The diabetes education intervention consists of four workshops delivered as 2-hour weekly sessions that include a diabetes educator and an automotive instructor:

In the first session, men learn about “starting and operating” their body with diabetes, and checking their “gauges” when it comes to blood pressure, cholesterol, and other measures, according to Dr. Concha.

The second session stresses the importance of physical activity (“using all your gears”) and of managing stress (“full throttle”).

The third session highlights medication as a tool (“to keep your battery charged”) and the importance of diabetes complications (“catastrophic failure”) as well as visiting the doctor (“tune ups and inspections”).

Finally, men learn about nutrition (high-performance fuel) in a workshop on eating well with diabetes. “We ask them to invite their family and friends, and they do,” said Dr. Concha.
 

Rubber hits the road

Since 2018, 16 workshops have been completed in El Paso, San Antonio, and Harlingen, Tex., of which 9 were in English, 5 were in Spanish, and 2 were bilingual. Due to the COVID-19 pandemic, 10 of the workshops were completed online, Dr. Concha said.

In total, 97 men engaged in the workshops, of whom 91% were Hispanic/Latino; 71% were employed, 71% were married, and 84% had health insurance. Eighty-six percent completed all four workshops, while 89% completed at least three workshops.

The number of days men measured food portions increased significantly from pre- to postworkshop assessment, from a mean of 2.1 days to 2.74 days, Dr. Concha reported. Similarly, the mean number of days counting carbohydrate portions increased significantly, from 1.92 to 2.64 days.

The proportion of men agreeing or strongly agreeing they were confident they could manage diabetes increased from 74% before the intervention to 93% afterward, according to Dr. Concha’s presentation.

By contrast, there were no statistically significant increases in physical outcomes including physical activity, weight, waist circumference, A1c, or blood pressure from before the workshop to after, though outcomes trended in an improved direction, according to Dr. Concha.

Postactivity satisfaction survey results showed that 86%of men said the automotive analogies in the program helped them understand the importance of diabetes management. “I am looking forward to better managing my human-mobile for a long, long time with a good quality of life,” one of the men wrote in survey feedback.

Dr. Concha and coauthors reported no conflicts of interest related to the study.

Automotive-themed workshops that refer to doctor visits as “tune-ups” and nutritious food as “high-performance fuel” are showing promise as a strategy to better explain diabetes self-management to Mexican American men, an investigator has reported.

Ronnie Kaufman/DigitalVision

The workshops, which started out in person and transitioned online because of the COVID-19 pandemic, have improved self-care behaviors among Mexican American men with diabetes, said Jeannie Belinda Concha, PhD, MPH, of the University of Texas, El Paso.

After participating in the workshops, known as The Diabetes Garage, men more often measured food portions and counted carbohydrates, and had improved confidence in their ability to self-manage their diabetes, Dr. Concha said in a virtual presentation on the study.

Although those improvements in self-care behaviors didn’t translate into significant improvements in blood pressure or hemoglobin A1c, she said, they could be predecessors to improved physical health outcomes with longer follow-up.

”We know it takes some time to move those numbers, but they are going in the right direction,” Dr. Concha said in her presentation, which took place during the annual scientific sessions of the American Diabetes Association.
 

Meeting Mexican American men where they’re at

Robert Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said The Diabetes Garage is an “innovative” approach to tailoring diabetes self-care message for a specific of individuals.

“It’s such a wonderful example of something that we believe so strongly, which is that you’ve got to meet people where they’re at,” Dr. Gabbay said in an interview.

“We know that people learn in different ways, and people and with different backgrounds have different things that resonate with them,” he continued. “For better or worse, one size doesn’t fit all, and that in a sense is one of the challenges around diabetes, because we’re really trying to help everybody.”
 

Unmet needs for diabetes education

The prevalence of diabetes in the United States is high among Hispanics, higher among Mexican Americans, and even higher still among Mexican-American men, according to Dr. Concha.

The age-adjusted prevalence of diabetes is 16.2% among Mexican-American men, as compared with 12.8% for Mexican American women, and 8.6% for White non-Hispanic men, according to 2018 data from the Centers for Disease Control and Prevention that Dr. Concha highlighted in her presentation.

Moreover, only 25% of participants in diabetes education are men, highlighting another disparity that needs to be addressed, she said.
 

Infusing diabetes self-management with car culture

The Diabetes Garage leverages a positive “car culture” that is prevalent in Mexican American communities in general, and cities like El Paso in particular, Dr. Concha said.

This culture brings Mexican American people together at numerous car shows, and is viewed as a form of family identification for enthusiasts, who will illustrate their own pride by customizing their cars with cultural symbols, according to Dr. Concha.

The diabetes education intervention consists of four workshops delivered as 2-hour weekly sessions that include a diabetes educator and an automotive instructor:

In the first session, men learn about “starting and operating” their body with diabetes, and checking their “gauges” when it comes to blood pressure, cholesterol, and other measures, according to Dr. Concha.

The second session stresses the importance of physical activity (“using all your gears”) and of managing stress (“full throttle”).

The third session highlights medication as a tool (“to keep your battery charged”) and the importance of diabetes complications (“catastrophic failure”) as well as visiting the doctor (“tune ups and inspections”).

Finally, men learn about nutrition (high-performance fuel) in a workshop on eating well with diabetes. “We ask them to invite their family and friends, and they do,” said Dr. Concha.
 

Rubber hits the road

Since 2018, 16 workshops have been completed in El Paso, San Antonio, and Harlingen, Tex., of which 9 were in English, 5 were in Spanish, and 2 were bilingual. Due to the COVID-19 pandemic, 10 of the workshops were completed online, Dr. Concha said.

In total, 97 men engaged in the workshops, of whom 91% were Hispanic/Latino; 71% were employed, 71% were married, and 84% had health insurance. Eighty-six percent completed all four workshops, while 89% completed at least three workshops.

The number of days men measured food portions increased significantly from pre- to postworkshop assessment, from a mean of 2.1 days to 2.74 days, Dr. Concha reported. Similarly, the mean number of days counting carbohydrate portions increased significantly, from 1.92 to 2.64 days.

The proportion of men agreeing or strongly agreeing they were confident they could manage diabetes increased from 74% before the intervention to 93% afterward, according to Dr. Concha’s presentation.

By contrast, there were no statistically significant increases in physical outcomes including physical activity, weight, waist circumference, A1c, or blood pressure from before the workshop to after, though outcomes trended in an improved direction, according to Dr. Concha.

Postactivity satisfaction survey results showed that 86%of men said the automotive analogies in the program helped them understand the importance of diabetes management. “I am looking forward to better managing my human-mobile for a long, long time with a good quality of life,” one of the men wrote in survey feedback.

Dr. Concha and coauthors reported no conflicts of interest related to the study.

Automotive-themed workshops that refer to doctor visits as “tune-ups” and nutritious food as “high-performance fuel” are showing promise as a strategy to better explain diabetes self-management to Mexican American men, an investigator has reported.

Ronnie Kaufman/DigitalVision

The workshops, which started out in person and transitioned online because of the COVID-19 pandemic, have improved self-care behaviors among Mexican American men with diabetes, said Jeannie Belinda Concha, PhD, MPH, of the University of Texas, El Paso.

After participating in the workshops, known as The Diabetes Garage, men more often measured food portions and counted carbohydrates, and had improved confidence in their ability to self-manage their diabetes, Dr. Concha said in a virtual presentation on the study.

Although those improvements in self-care behaviors didn’t translate into significant improvements in blood pressure or hemoglobin A1c, she said, they could be predecessors to improved physical health outcomes with longer follow-up.

”We know it takes some time to move those numbers, but they are going in the right direction,” Dr. Concha said in her presentation, which took place during the annual scientific sessions of the American Diabetes Association.
 

Meeting Mexican American men where they’re at

Robert Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said The Diabetes Garage is an “innovative” approach to tailoring diabetes self-care message for a specific of individuals.

“It’s such a wonderful example of something that we believe so strongly, which is that you’ve got to meet people where they’re at,” Dr. Gabbay said in an interview.

“We know that people learn in different ways, and people and with different backgrounds have different things that resonate with them,” he continued. “For better or worse, one size doesn’t fit all, and that in a sense is one of the challenges around diabetes, because we’re really trying to help everybody.”
 

Unmet needs for diabetes education

The prevalence of diabetes in the United States is high among Hispanics, higher among Mexican Americans, and even higher still among Mexican-American men, according to Dr. Concha.

The age-adjusted prevalence of diabetes is 16.2% among Mexican-American men, as compared with 12.8% for Mexican American women, and 8.6% for White non-Hispanic men, according to 2018 data from the Centers for Disease Control and Prevention that Dr. Concha highlighted in her presentation.

Moreover, only 25% of participants in diabetes education are men, highlighting another disparity that needs to be addressed, she said.
 

Infusing diabetes self-management with car culture

The Diabetes Garage leverages a positive “car culture” that is prevalent in Mexican American communities in general, and cities like El Paso in particular, Dr. Concha said.

This culture brings Mexican American people together at numerous car shows, and is viewed as a form of family identification for enthusiasts, who will illustrate their own pride by customizing their cars with cultural symbols, according to Dr. Concha.

The diabetes education intervention consists of four workshops delivered as 2-hour weekly sessions that include a diabetes educator and an automotive instructor:

In the first session, men learn about “starting and operating” their body with diabetes, and checking their “gauges” when it comes to blood pressure, cholesterol, and other measures, according to Dr. Concha.

The second session stresses the importance of physical activity (“using all your gears”) and of managing stress (“full throttle”).

The third session highlights medication as a tool (“to keep your battery charged”) and the importance of diabetes complications (“catastrophic failure”) as well as visiting the doctor (“tune ups and inspections”).

Finally, men learn about nutrition (high-performance fuel) in a workshop on eating well with diabetes. “We ask them to invite their family and friends, and they do,” said Dr. Concha.
 

Rubber hits the road

Since 2018, 16 workshops have been completed in El Paso, San Antonio, and Harlingen, Tex., of which 9 were in English, 5 were in Spanish, and 2 were bilingual. Due to the COVID-19 pandemic, 10 of the workshops were completed online, Dr. Concha said.

In total, 97 men engaged in the workshops, of whom 91% were Hispanic/Latino; 71% were employed, 71% were married, and 84% had health insurance. Eighty-six percent completed all four workshops, while 89% completed at least three workshops.

The number of days men measured food portions increased significantly from pre- to postworkshop assessment, from a mean of 2.1 days to 2.74 days, Dr. Concha reported. Similarly, the mean number of days counting carbohydrate portions increased significantly, from 1.92 to 2.64 days.

The proportion of men agreeing or strongly agreeing they were confident they could manage diabetes increased from 74% before the intervention to 93% afterward, according to Dr. Concha’s presentation.

By contrast, there were no statistically significant increases in physical outcomes including physical activity, weight, waist circumference, A1c, or blood pressure from before the workshop to after, though outcomes trended in an improved direction, according to Dr. Concha.

Postactivity satisfaction survey results showed that 86%of men said the automotive analogies in the program helped them understand the importance of diabetes management. “I am looking forward to better managing my human-mobile for a long, long time with a good quality of life,” one of the men wrote in survey feedback.

Dr. Concha and coauthors reported no conflicts of interest related to the study.

Patients with type 1 diabetes who used insulin degludec as their basal insulin had fewer than half the number of nocturnal hypoglycemia events, compared with patients who used insulin glargine U100, in a head-to-head crossover study with 51 patients who had a history of nighttime hypoglycemia episodes.

Patients with type 1 diabetes who are “struggling with nocturnal hypoglycemia would benefit from insulin degludec treatment,” said Julie M. Brøsen, MD, at the annual scientific sessions of the American Diabetes Association.
 

Accumulating evidence for less hypoglycemia with insulin degludec

Results from several studies comparing insulin degludec (Tresiba), a second-generation, longer-acting insulin with more stable steady-state performance, with the first-generation basal insulin analogue glargine (Lantus), have built the case that degludec produces fewer hypoglycemia events.

The landmark SWITCH 1 crossover study published in 2017 showed in about 500 patients with type 1 diabetes and a risk factor for hypoglycemia that treatment with insulin degludec led to significantly few total hypoglycemia episodes and significantly fewer nocturnal episodes, compared with insulin glargine.

Next came similar findings from ReFLeCT, a multicenter observational study that followed 556 unselected patients with type 1 diabetes in routine practice settings who switched to insulin degludec following treatment with a different basal insulin. The results again showed a significant drop-off in total, nonsevere, severe, and nocturnal hypoglycemia events.
 

Homing in on higher-risk patients

The current study, HypoDeg (Insulin Degludec and Symptomatic Nocturnal Hypoglycaemia), ran at 10 Danish centers and enrolled 149 adults with type 1 diabetes who had at least one episode of severe nocturnal hypoglycemia within the prior 2 years, focusing on patients most at risk for future nocturnal hypoglycemia events. In an unusual study design, researchers identified nocturnal hypoglycemic episodes with hourly venous blood samples drawn from a subcutaneous line.

They randomized the patients to basal insulin treatment with either insulin degludec or to insulin glargine U100, allowed their treatment to stabilize for 3 months, and then tallied nocturnal hypoglycemia events for 9 months. They then crossed patients to the alternative basal insulin and repeated the process.

Results from the full study have not yet appeared in published form but were in a pair of reports at the 2020 scientific sessions of the ADA.

One report included findings based on 136 episodes of severe hypoglycemia identified clinically and showed these events occurred 35% less often during treatment with insulin degludec, a significant difference. The overall finding was primarily driven by 48% fewer episodes of severe nocturnal hypoglycemia, but this difference was not significant.

The second report identified hypoglycemia events with continuous glucose monitoring in 74 of the study participants, which identified 193 episodes of nonsevere nocturnal hypoglycemia and found that treatment with insulin degludec cut the rate by 47%, primarily by reducing asymptomatic episodes.

Hourly blood draws track overnight hypoglycemia

The current study included 51 of the 149 HypoDeg patients who agreed to undergo overnight blood sampling and had this done at least once while treated with each of the two study insulins. (The study design called for two blood sampling nights for each willing patient during each of the two treatment periods.) The 51 patients had type 1 diabetes for an average of 28 years and an average age of 58 years. Two-thirds were men, their baseline A1c was 7.8%, and on average had 2.6 episodes of severe nocturnal hypoglycemia during the prior 2 years.

The researchers drew hourly blood specimens on a total of 196 nights from the 51 participating patients and identified 57 nights when blood glucose levels reached hypoglycemia thresholds in 33 patients. One-third of the events occurred when patients were on insulin degludec treatment, and two-thirds when they were on insulin glargine, reported Dr. Brøsen.

She presented three separate analyses of the data. One analysis focused on level 1 hypoglycemia events, when blood glucose dips to 70 mg/dL or less, which occurred 54% less often when patients were on insulin degludec. A second analysis looked at level 2 events, when blood glucose falls below 54 mg/dL, and treatment with insulin degludec cut this by 64% compared with insulin glargine. The third analysis focused on symptomatic events when blood glucose was 70 mg/dL or less, and treatment with insulin degludec linked with a 62% cut in this metric. All three between-group differences were significant.
 

Evidence supports already-changed practice

This new evidence “supports recommending” insulin degludec over insulin glargine, commented Bastiaan E. de Galan, MD, PhD, an endocrinologist and professor at Maastrict (the Netherlands) University Medical Center. The new results “extend those from previous trials in populations with type 1 diabetes that were unselected for the risk of hypoglycemia. In clinical practice, insulin degludec is already considered for patients who reported nocturnal hypoglycemia while on insulin glargine U100, but it’s great this study provides the scientific evidence,” said Dr. de Galan in an interview.

“The lower rate of nocturnal hypoglycemia with degludec, compared with glargine U100 is well established. Inpatient assessment of hypoglycemia with measurement of hourly plasma glucose allowed HypoDeg to provide stronger evidence than prior studies. The benefit of delgudec versus glargine U100 was significant and clinically meaningful, in hypo-prone patients who would benefit the most” by using insulin degludec, commented Gian Paolo Fadini, MD, an endocrinologist at the University of Padova (Italy), and a lead investigator on the ReFLeCT study.

But insulin degludec is not a completely silver bullet. Its prolonged duration of action and stability that may in part explain why it limits hypoglycemia events can also be a drawback: “It probably offers fewer options for flexibility. Any change in dose takes at least a day or 2 to settle, which may be unfavorable in certain circumstances,” noted Dr. de Galan.

“I wouldn’t recommend insulin degludec for all patients with type 1 diabetes. It’s an individual evaluation in each patient,” said Dr. Brøsen. “We will be looking into whether some patients are better off on insulin glargine.”
 

Cost makes a difference

Another, potentially more consequential flaw is insulin degludec’s relative expense.

“To date, use of degludec in routine practice has been limited by its cost, compared with older basal insulins,” observed Dr. Fadini in an interview. “In several countries, including the United States, degludec is substantially more expensive than glargine.”

The ADA’s Standards of Medical Care in Diabetes–2021 includes table 9.3 that lists the costs of various insulins and shows the median average wholesale price of insulin glargine U100 follow-on products as $190/vial, compared with a $407 price for a similar vial of insulin degludec.

Insulin degludec “is clearly superior from a hypoglycemia standpoint. Patients with type 1 diabetes like the reduction because hypoglycemia is scary, and dangerous. The main issue is cost, and the extent to which it may be covered by insurance,” commented Lisa Chow, MD, an endocrinologist at the University of Minnesota, Minneapolis. “We generally won’t prescribe degludec unless it is at a price affordable to the patient. We try to use patient assistance programs sponsored by the company [that markets insulin degludec: Novo Nordisk] to try to make it more affordable.”

Dr. Chow also highlighted that a new wrinkle has been introduction of a more concentrated formulation of insulin glargine, U300, which appears to cause less hypoglycemia than insulin glargine U100. Recent study results indicated that no significant difference exists in the incidence of hypoglycemia among patients treated with insulin glargine U300 and those treated with insulin degludec, such as findings from the BRIGHT trial, which included just over 900 patients, and in the CONCLUDE trial, which randomized more than 1,600 patients.

The HypoDeg study was sponsored by Novo Nordisk, the company that markets insulin degludec. Dr. Brøsen had no personal disclosures, but several of her coauthors were either Novo Nordisk employees or had financial relationships with the company. Dr. de Galan has received research funding from Novo Nordisk. Dr. Fadini has received lecture fees and research funding from Novo Nordisk, from Sanofi, the company that markets insulin glargine, and from several other companies. Dr. Chow has received research funding from Dexcom.

mzoler@mdedge.com

Patients with type 1 diabetes who used insulin degludec as their basal insulin had fewer than half the number of nocturnal hypoglycemia events, compared with patients who used insulin glargine U100, in a head-to-head crossover study with 51 patients who had a history of nighttime hypoglycemia episodes.

Patients with type 1 diabetes who are “struggling with nocturnal hypoglycemia would benefit from insulin degludec treatment,” said Julie M. Brøsen, MD, at the annual scientific sessions of the American Diabetes Association.
 

Accumulating evidence for less hypoglycemia with insulin degludec

Results from several studies comparing insulin degludec (Tresiba), a second-generation, longer-acting insulin with more stable steady-state performance, with the first-generation basal insulin analogue glargine (Lantus), have built the case that degludec produces fewer hypoglycemia events.

The landmark SWITCH 1 crossover study published in 2017 showed in about 500 patients with type 1 diabetes and a risk factor for hypoglycemia that treatment with insulin degludec led to significantly few total hypoglycemia episodes and significantly fewer nocturnal episodes, compared with insulin glargine.

Next came similar findings from ReFLeCT, a multicenter observational study that followed 556 unselected patients with type 1 diabetes in routine practice settings who switched to insulin degludec following treatment with a different basal insulin. The results again showed a significant drop-off in total, nonsevere, severe, and nocturnal hypoglycemia events.
 

Homing in on higher-risk patients

The current study, HypoDeg (Insulin Degludec and Symptomatic Nocturnal Hypoglycaemia), ran at 10 Danish centers and enrolled 149 adults with type 1 diabetes who had at least one episode of severe nocturnal hypoglycemia within the prior 2 years, focusing on patients most at risk for future nocturnal hypoglycemia events. In an unusual study design, researchers identified nocturnal hypoglycemic episodes with hourly venous blood samples drawn from a subcutaneous line.

They randomized the patients to basal insulin treatment with either insulin degludec or to insulin glargine U100, allowed their treatment to stabilize for 3 months, and then tallied nocturnal hypoglycemia events for 9 months. They then crossed patients to the alternative basal insulin and repeated the process.

Results from the full study have not yet appeared in published form but were in a pair of reports at the 2020 scientific sessions of the ADA.

One report included findings based on 136 episodes of severe hypoglycemia identified clinically and showed these events occurred 35% less often during treatment with insulin degludec, a significant difference. The overall finding was primarily driven by 48% fewer episodes of severe nocturnal hypoglycemia, but this difference was not significant.

The second report identified hypoglycemia events with continuous glucose monitoring in 74 of the study participants, which identified 193 episodes of nonsevere nocturnal hypoglycemia and found that treatment with insulin degludec cut the rate by 47%, primarily by reducing asymptomatic episodes.

Hourly blood draws track overnight hypoglycemia

The current study included 51 of the 149 HypoDeg patients who agreed to undergo overnight blood sampling and had this done at least once while treated with each of the two study insulins. (The study design called for two blood sampling nights for each willing patient during each of the two treatment periods.) The 51 patients had type 1 diabetes for an average of 28 years and an average age of 58 years. Two-thirds were men, their baseline A1c was 7.8%, and on average had 2.6 episodes of severe nocturnal hypoglycemia during the prior 2 years.

The researchers drew hourly blood specimens on a total of 196 nights from the 51 participating patients and identified 57 nights when blood glucose levels reached hypoglycemia thresholds in 33 patients. One-third of the events occurred when patients were on insulin degludec treatment, and two-thirds when they were on insulin glargine, reported Dr. Brøsen.

She presented three separate analyses of the data. One analysis focused on level 1 hypoglycemia events, when blood glucose dips to 70 mg/dL or less, which occurred 54% less often when patients were on insulin degludec. A second analysis looked at level 2 events, when blood glucose falls below 54 mg/dL, and treatment with insulin degludec cut this by 64% compared with insulin glargine. The third analysis focused on symptomatic events when blood glucose was 70 mg/dL or less, and treatment with insulin degludec linked with a 62% cut in this metric. All three between-group differences were significant.
 

Evidence supports already-changed practice

This new evidence “supports recommending” insulin degludec over insulin glargine, commented Bastiaan E. de Galan, MD, PhD, an endocrinologist and professor at Maastrict (the Netherlands) University Medical Center. The new results “extend those from previous trials in populations with type 1 diabetes that were unselected for the risk of hypoglycemia. In clinical practice, insulin degludec is already considered for patients who reported nocturnal hypoglycemia while on insulin glargine U100, but it’s great this study provides the scientific evidence,” said Dr. de Galan in an interview.

“The lower rate of nocturnal hypoglycemia with degludec, compared with glargine U100 is well established. Inpatient assessment of hypoglycemia with measurement of hourly plasma glucose allowed HypoDeg to provide stronger evidence than prior studies. The benefit of delgudec versus glargine U100 was significant and clinically meaningful, in hypo-prone patients who would benefit the most” by using insulin degludec, commented Gian Paolo Fadini, MD, an endocrinologist at the University of Padova (Italy), and a lead investigator on the ReFLeCT study.

But insulin degludec is not a completely silver bullet. Its prolonged duration of action and stability that may in part explain why it limits hypoglycemia events can also be a drawback: “It probably offers fewer options for flexibility. Any change in dose takes at least a day or 2 to settle, which may be unfavorable in certain circumstances,” noted Dr. de Galan.

“I wouldn’t recommend insulin degludec for all patients with type 1 diabetes. It’s an individual evaluation in each patient,” said Dr. Brøsen. “We will be looking into whether some patients are better off on insulin glargine.”
 

Cost makes a difference

Another, potentially more consequential flaw is insulin degludec’s relative expense.

“To date, use of degludec in routine practice has been limited by its cost, compared with older basal insulins,” observed Dr. Fadini in an interview. “In several countries, including the United States, degludec is substantially more expensive than glargine.”

The ADA’s Standards of Medical Care in Diabetes–2021 includes table 9.3 that lists the costs of various insulins and shows the median average wholesale price of insulin glargine U100 follow-on products as $190/vial, compared with a $407 price for a similar vial of insulin degludec.

Insulin degludec “is clearly superior from a hypoglycemia standpoint. Patients with type 1 diabetes like the reduction because hypoglycemia is scary, and dangerous. The main issue is cost, and the extent to which it may be covered by insurance,” commented Lisa Chow, MD, an endocrinologist at the University of Minnesota, Minneapolis. “We generally won’t prescribe degludec unless it is at a price affordable to the patient. We try to use patient assistance programs sponsored by the company [that markets insulin degludec: Novo Nordisk] to try to make it more affordable.”

Dr. Chow also highlighted that a new wrinkle has been introduction of a more concentrated formulation of insulin glargine, U300, which appears to cause less hypoglycemia than insulin glargine U100. Recent study results indicated that no significant difference exists in the incidence of hypoglycemia among patients treated with insulin glargine U300 and those treated with insulin degludec, such as findings from the BRIGHT trial, which included just over 900 patients, and in the CONCLUDE trial, which randomized more than 1,600 patients.

The HypoDeg study was sponsored by Novo Nordisk, the company that markets insulin degludec. Dr. Brøsen had no personal disclosures, but several of her coauthors were either Novo Nordisk employees or had financial relationships with the company. Dr. de Galan has received research funding from Novo Nordisk. Dr. Fadini has received lecture fees and research funding from Novo Nordisk, from Sanofi, the company that markets insulin glargine, and from several other companies. Dr. Chow has received research funding from Dexcom.

mzoler@mdedge.com

Patients with type 1 diabetes who used insulin degludec as their basal insulin had fewer than half the number of nocturnal hypoglycemia events, compared with patients who used insulin glargine U100, in a head-to-head crossover study with 51 patients who had a history of nighttime hypoglycemia episodes.

Patients with type 1 diabetes who are “struggling with nocturnal hypoglycemia would benefit from insulin degludec treatment,” said Julie M. Brøsen, MD, at the annual scientific sessions of the American Diabetes Association.
 

Accumulating evidence for less hypoglycemia with insulin degludec

Results from several studies comparing insulin degludec (Tresiba), a second-generation, longer-acting insulin with more stable steady-state performance, with the first-generation basal insulin analogue glargine (Lantus), have built the case that degludec produces fewer hypoglycemia events.

The landmark SWITCH 1 crossover study published in 2017 showed in about 500 patients with type 1 diabetes and a risk factor for hypoglycemia that treatment with insulin degludec led to significantly few total hypoglycemia episodes and significantly fewer nocturnal episodes, compared with insulin glargine.

Next came similar findings from ReFLeCT, a multicenter observational study that followed 556 unselected patients with type 1 diabetes in routine practice settings who switched to insulin degludec following treatment with a different basal insulin. The results again showed a significant drop-off in total, nonsevere, severe, and nocturnal hypoglycemia events.
 

Homing in on higher-risk patients

The current study, HypoDeg (Insulin Degludec and Symptomatic Nocturnal Hypoglycaemia), ran at 10 Danish centers and enrolled 149 adults with type 1 diabetes who had at least one episode of severe nocturnal hypoglycemia within the prior 2 years, focusing on patients most at risk for future nocturnal hypoglycemia events. In an unusual study design, researchers identified nocturnal hypoglycemic episodes with hourly venous blood samples drawn from a subcutaneous line.

They randomized the patients to basal insulin treatment with either insulin degludec or to insulin glargine U100, allowed their treatment to stabilize for 3 months, and then tallied nocturnal hypoglycemia events for 9 months. They then crossed patients to the alternative basal insulin and repeated the process.

Results from the full study have not yet appeared in published form but were in a pair of reports at the 2020 scientific sessions of the ADA.

One report included findings based on 136 episodes of severe hypoglycemia identified clinically and showed these events occurred 35% less often during treatment with insulin degludec, a significant difference. The overall finding was primarily driven by 48% fewer episodes of severe nocturnal hypoglycemia, but this difference was not significant.

The second report identified hypoglycemia events with continuous glucose monitoring in 74 of the study participants, which identified 193 episodes of nonsevere nocturnal hypoglycemia and found that treatment with insulin degludec cut the rate by 47%, primarily by reducing asymptomatic episodes.

Hourly blood draws track overnight hypoglycemia

The current study included 51 of the 149 HypoDeg patients who agreed to undergo overnight blood sampling and had this done at least once while treated with each of the two study insulins. (The study design called for two blood sampling nights for each willing patient during each of the two treatment periods.) The 51 patients had type 1 diabetes for an average of 28 years and an average age of 58 years. Two-thirds were men, their baseline A1c was 7.8%, and on average had 2.6 episodes of severe nocturnal hypoglycemia during the prior 2 years.

The researchers drew hourly blood specimens on a total of 196 nights from the 51 participating patients and identified 57 nights when blood glucose levels reached hypoglycemia thresholds in 33 patients. One-third of the events occurred when patients were on insulin degludec treatment, and two-thirds when they were on insulin glargine, reported Dr. Brøsen.

She presented three separate analyses of the data. One analysis focused on level 1 hypoglycemia events, when blood glucose dips to 70 mg/dL or less, which occurred 54% less often when patients were on insulin degludec. A second analysis looked at level 2 events, when blood glucose falls below 54 mg/dL, and treatment with insulin degludec cut this by 64% compared with insulin glargine. The third analysis focused on symptomatic events when blood glucose was 70 mg/dL or less, and treatment with insulin degludec linked with a 62% cut in this metric. All three between-group differences were significant.
 

Evidence supports already-changed practice

This new evidence “supports recommending” insulin degludec over insulin glargine, commented Bastiaan E. de Galan, MD, PhD, an endocrinologist and professor at Maastrict (the Netherlands) University Medical Center. The new results “extend those from previous trials in populations with type 1 diabetes that were unselected for the risk of hypoglycemia. In clinical practice, insulin degludec is already considered for patients who reported nocturnal hypoglycemia while on insulin glargine U100, but it’s great this study provides the scientific evidence,” said Dr. de Galan in an interview.

“The lower rate of nocturnal hypoglycemia with degludec, compared with glargine U100 is well established. Inpatient assessment of hypoglycemia with measurement of hourly plasma glucose allowed HypoDeg to provide stronger evidence than prior studies. The benefit of delgudec versus glargine U100 was significant and clinically meaningful, in hypo-prone patients who would benefit the most” by using insulin degludec, commented Gian Paolo Fadini, MD, an endocrinologist at the University of Padova (Italy), and a lead investigator on the ReFLeCT study.

But insulin degludec is not a completely silver bullet. Its prolonged duration of action and stability that may in part explain why it limits hypoglycemia events can also be a drawback: “It probably offers fewer options for flexibility. Any change in dose takes at least a day or 2 to settle, which may be unfavorable in certain circumstances,” noted Dr. de Galan.

“I wouldn’t recommend insulin degludec for all patients with type 1 diabetes. It’s an individual evaluation in each patient,” said Dr. Brøsen. “We will be looking into whether some patients are better off on insulin glargine.”
 

Cost makes a difference

Another, potentially more consequential flaw is insulin degludec’s relative expense.

“To date, use of degludec in routine practice has been limited by its cost, compared with older basal insulins,” observed Dr. Fadini in an interview. “In several countries, including the United States, degludec is substantially more expensive than glargine.”

The ADA’s Standards of Medical Care in Diabetes–2021 includes table 9.3 that lists the costs of various insulins and shows the median average wholesale price of insulin glargine U100 follow-on products as $190/vial, compared with a $407 price for a similar vial of insulin degludec.

Insulin degludec “is clearly superior from a hypoglycemia standpoint. Patients with type 1 diabetes like the reduction because hypoglycemia is scary, and dangerous. The main issue is cost, and the extent to which it may be covered by insurance,” commented Lisa Chow, MD, an endocrinologist at the University of Minnesota, Minneapolis. “We generally won’t prescribe degludec unless it is at a price affordable to the patient. We try to use patient assistance programs sponsored by the company [that markets insulin degludec: Novo Nordisk] to try to make it more affordable.”

Dr. Chow also highlighted that a new wrinkle has been introduction of a more concentrated formulation of insulin glargine, U300, which appears to cause less hypoglycemia than insulin glargine U100. Recent study results indicated that no significant difference exists in the incidence of hypoglycemia among patients treated with insulin glargine U300 and those treated with insulin degludec, such as findings from the BRIGHT trial, which included just over 900 patients, and in the CONCLUDE trial, which randomized more than 1,600 patients.

The HypoDeg study was sponsored by Novo Nordisk, the company that markets insulin degludec. Dr. Brøsen had no personal disclosures, but several of her coauthors were either Novo Nordisk employees or had financial relationships with the company. Dr. de Galan has received research funding from Novo Nordisk. Dr. Fadini has received lecture fees and research funding from Novo Nordisk, from Sanofi, the company that markets insulin glargine, and from several other companies. Dr. Chow has received research funding from Dexcom.

mzoler@mdedge.com

A single, simple question about sleep habits asked to people with diabetes in the UK Biobank database identified a subgroup with a nearly doubled mortality rate during almost 9 years of follow-up: those who said they usually had sleep disturbances.

The question was: Do you never, rarely, sometimes, or usually have trouble falling asleep, or waking in the middle of the night?

Adults in the UK Biobank with any form of self-reported diabetes or insulin use who answered that they usually have sleep disturbances had a significant 87% higher mortality rate than did those without diabetes who said they never or rarely had sleep disturbances, in a fully adjusted model with an average follow-up of 8.9 years, Kristen L. Knutson, PhD, and coauthors reported in the Journal of Sleep Research.

Mortality was 11% higher in respondents who reported frequent sleep disturbances but had no diabetes than in those without frequent sleep disturbances. Furthermore, those with diabetes but without frequent sleep disturbances had a 67% higher mortality rate, compared with those without diabetes. Both differences were statistically significant in a model that adjusted for age, sex, ethnicity, smoking, sleep duration, body mass index, and other covariates.

The findings suggest that diabetes and frequent sleep disturbances act in a roughly additive way to raise mortality risk, said Dr. Knutson, an epidemiologist and neurologist who specializes in sleep medicine at Northwestern University, Chicago.

She suggested that, based on these findings, clinicians should consider annually asking patients with diabetes this key question about the frequency of their sleep disturbances. They should then follow up with patients who report usual disturbances by referring them to a sleep clinic to test for a sleep disorders such as insomnia or sleep apnea. Sleep apnea especially is “particularly common in patients with type 2 diabetes,” Dr. Knutson noted in an interview.
 

A need to ‘spread awareness’ about diabetes and disturbed sleep.

The study run by Dr. Knutson and associates “is one of the largest population-based studies” to examine the relationship between sleep disturbances, diabetes, and mortality, commented Sirimon Reutrakul, MD, an endocrinologist and diabetes specialist at the University of Illinois Hospital in Chicago.

“This study highlights the detrimental effects of sleep disturbances in people with or without diabetes, and adds to the effects of sleep disturbances such as insomnia symptoms. People with diabetes often have sleep disturbances. Obstructive sleep apnea is very common in people with diabetes, and insomnia symptoms could be present in people with obstructive sleep apnea or it could be a separate problem,” Dr. Reutrakul said in an interview. Sleep disturbances can arise from direct effects of diabetes, such as nocturia, worry about glucose levels, pain, depressive symptoms, and anxiety, or can result from comorbidities that interfere with sleep.

“It is prudent to ask patients with diabetes about sleep patterns,” said Dr. Reutrakul, and she endorsed the specific question that Dr. Knutson recommended asking patients. Other aspects of sleep quality that could be helpful for a diagnosis include sleep duration, sleep timing, and snoring. “Some physicians ask these questions, but we need to spread awareness,” she added.

Prior to referring patients to a sleep clinic, Dr. Reutrakul suggested that clinicians could also assess possible triggers such as inadequate glucose control, pain, and anxiety, and they could also recommend good sleep hygiene strategies such as what’s recommended by the Sleep Foundation.
 

Sleep disturbances ‘highly prevalent’ among U.K. adults.

The UK Biobank enrolled just over 500,000 people aged 37-73 years during 2006-2010, and 487,728 of these people had data available that allowed their inclusion in the analysis. That group averaged about 57 years of age, 54% were women, 94% were White, and their average body mass index was 27-28 kg/m2.

More than a quarter of these people reported having “usual” sleep disturbances, showing that sleep disturbances are “highly prevalent” among U.K. residents, noted the authors. Just under a quarter of the subjects reported they never or rarely had sleep disturbances, and the remaining half of subjects said they “sometimes” had sleep disturbances.

In addition, 69% reported neither diabetes nor frequent sleep disturbances, 26% had frequent sleep disturbances but no diabetes, 3% had diabetes but not frequent sleep disturbances, and 2% had both diabetes and frequent sleep disturbances.

During the average 8.9-year follow-up, 19,177 people died from any cause (4%), and 3,874 of these deaths involved cardiovascular disease causes. Despite the significant association of diabetes and frequent sleep disturbances with an increased rate of all-cause mortality, the same combination showed no significant link with cardiovascular mortality in the study’s full-adjusted model. This may be because “frequent sleep disturbances can lead to a variety of causes of death,” Dr. Knutson suggested.

The information collected by the UK Biobank did not allow the researchers to distinguish between type 1 and type 2 diabetes.

The findings “suggest that regardless of the cause of sleep disturbance, reporting sleep disturbances on a frequent basis is an important signal of elevated risk of mortality. Such symptoms should therefore be investigated further by physicians, particularly in patients who have also been diagnosed with diabetes,” wrote Dr. Knutson and coauthors. “This is the first study to examine the effect of the combination of insomnia and diabetes on mortality risk.”

But Dr. Knutson highlighted that “sleep problems are important for everyone, not just people with diabetes.

Neither Dr. Knutson and coauthors nor Dr. Reutrakul had no disclosures.

mzoler@mdedge.com

A single, simple question about sleep habits asked to people with diabetes in the UK Biobank database identified a subgroup with a nearly doubled mortality rate during almost 9 years of follow-up: those who said they usually had sleep disturbances.

The question was: Do you never, rarely, sometimes, or usually have trouble falling asleep, or waking in the middle of the night?

Adults in the UK Biobank with any form of self-reported diabetes or insulin use who answered that they usually have sleep disturbances had a significant 87% higher mortality rate than did those without diabetes who said they never or rarely had sleep disturbances, in a fully adjusted model with an average follow-up of 8.9 years, Kristen L. Knutson, PhD, and coauthors reported in the Journal of Sleep Research.

Mortality was 11% higher in respondents who reported frequent sleep disturbances but had no diabetes than in those without frequent sleep disturbances. Furthermore, those with diabetes but without frequent sleep disturbances had a 67% higher mortality rate, compared with those without diabetes. Both differences were statistically significant in a model that adjusted for age, sex, ethnicity, smoking, sleep duration, body mass index, and other covariates.

The findings suggest that diabetes and frequent sleep disturbances act in a roughly additive way to raise mortality risk, said Dr. Knutson, an epidemiologist and neurologist who specializes in sleep medicine at Northwestern University, Chicago.

She suggested that, based on these findings, clinicians should consider annually asking patients with diabetes this key question about the frequency of their sleep disturbances. They should then follow up with patients who report usual disturbances by referring them to a sleep clinic to test for a sleep disorders such as insomnia or sleep apnea. Sleep apnea especially is “particularly common in patients with type 2 diabetes,” Dr. Knutson noted in an interview.
 

A need to ‘spread awareness’ about diabetes and disturbed sleep.

The study run by Dr. Knutson and associates “is one of the largest population-based studies” to examine the relationship between sleep disturbances, diabetes, and mortality, commented Sirimon Reutrakul, MD, an endocrinologist and diabetes specialist at the University of Illinois Hospital in Chicago.

“This study highlights the detrimental effects of sleep disturbances in people with or without diabetes, and adds to the effects of sleep disturbances such as insomnia symptoms. People with diabetes often have sleep disturbances. Obstructive sleep apnea is very common in people with diabetes, and insomnia symptoms could be present in people with obstructive sleep apnea or it could be a separate problem,” Dr. Reutrakul said in an interview. Sleep disturbances can arise from direct effects of diabetes, such as nocturia, worry about glucose levels, pain, depressive symptoms, and anxiety, or can result from comorbidities that interfere with sleep.

“It is prudent to ask patients with diabetes about sleep patterns,” said Dr. Reutrakul, and she endorsed the specific question that Dr. Knutson recommended asking patients. Other aspects of sleep quality that could be helpful for a diagnosis include sleep duration, sleep timing, and snoring. “Some physicians ask these questions, but we need to spread awareness,” she added.

Prior to referring patients to a sleep clinic, Dr. Reutrakul suggested that clinicians could also assess possible triggers such as inadequate glucose control, pain, and anxiety, and they could also recommend good sleep hygiene strategies such as what’s recommended by the Sleep Foundation.
 

Sleep disturbances ‘highly prevalent’ among U.K. adults.

The UK Biobank enrolled just over 500,000 people aged 37-73 years during 2006-2010, and 487,728 of these people had data available that allowed their inclusion in the analysis. That group averaged about 57 years of age, 54% were women, 94% were White, and their average body mass index was 27-28 kg/m2.

More than a quarter of these people reported having “usual” sleep disturbances, showing that sleep disturbances are “highly prevalent” among U.K. residents, noted the authors. Just under a quarter of the subjects reported they never or rarely had sleep disturbances, and the remaining half of subjects said they “sometimes” had sleep disturbances.

In addition, 69% reported neither diabetes nor frequent sleep disturbances, 26% had frequent sleep disturbances but no diabetes, 3% had diabetes but not frequent sleep disturbances, and 2% had both diabetes and frequent sleep disturbances.

During the average 8.9-year follow-up, 19,177 people died from any cause (4%), and 3,874 of these deaths involved cardiovascular disease causes. Despite the significant association of diabetes and frequent sleep disturbances with an increased rate of all-cause mortality, the same combination showed no significant link with cardiovascular mortality in the study’s full-adjusted model. This may be because “frequent sleep disturbances can lead to a variety of causes of death,” Dr. Knutson suggested.

The information collected by the UK Biobank did not allow the researchers to distinguish between type 1 and type 2 diabetes.

The findings “suggest that regardless of the cause of sleep disturbance, reporting sleep disturbances on a frequent basis is an important signal of elevated risk of mortality. Such symptoms should therefore be investigated further by physicians, particularly in patients who have also been diagnosed with diabetes,” wrote Dr. Knutson and coauthors. “This is the first study to examine the effect of the combination of insomnia and diabetes on mortality risk.”

But Dr. Knutson highlighted that “sleep problems are important for everyone, not just people with diabetes.

Neither Dr. Knutson and coauthors nor Dr. Reutrakul had no disclosures.

mzoler@mdedge.com

A single, simple question about sleep habits asked to people with diabetes in the UK Biobank database identified a subgroup with a nearly doubled mortality rate during almost 9 years of follow-up: those who said they usually had sleep disturbances.

The question was: Do you never, rarely, sometimes, or usually have trouble falling asleep, or waking in the middle of the night?

Adults in the UK Biobank with any form of self-reported diabetes or insulin use who answered that they usually have sleep disturbances had a significant 87% higher mortality rate than did those without diabetes who said they never or rarely had sleep disturbances, in a fully adjusted model with an average follow-up of 8.9 years, Kristen L. Knutson, PhD, and coauthors reported in the Journal of Sleep Research.

Mortality was 11% higher in respondents who reported frequent sleep disturbances but had no diabetes than in those without frequent sleep disturbances. Furthermore, those with diabetes but without frequent sleep disturbances had a 67% higher mortality rate, compared with those without diabetes. Both differences were statistically significant in a model that adjusted for age, sex, ethnicity, smoking, sleep duration, body mass index, and other covariates.

The findings suggest that diabetes and frequent sleep disturbances act in a roughly additive way to raise mortality risk, said Dr. Knutson, an epidemiologist and neurologist who specializes in sleep medicine at Northwestern University, Chicago.

She suggested that, based on these findings, clinicians should consider annually asking patients with diabetes this key question about the frequency of their sleep disturbances. They should then follow up with patients who report usual disturbances by referring them to a sleep clinic to test for a sleep disorders such as insomnia or sleep apnea. Sleep apnea especially is “particularly common in patients with type 2 diabetes,” Dr. Knutson noted in an interview.
 

A need to ‘spread awareness’ about diabetes and disturbed sleep.

The study run by Dr. Knutson and associates “is one of the largest population-based studies” to examine the relationship between sleep disturbances, diabetes, and mortality, commented Sirimon Reutrakul, MD, an endocrinologist and diabetes specialist at the University of Illinois Hospital in Chicago.

“This study highlights the detrimental effects of sleep disturbances in people with or without diabetes, and adds to the effects of sleep disturbances such as insomnia symptoms. People with diabetes often have sleep disturbances. Obstructive sleep apnea is very common in people with diabetes, and insomnia symptoms could be present in people with obstructive sleep apnea or it could be a separate problem,” Dr. Reutrakul said in an interview. Sleep disturbances can arise from direct effects of diabetes, such as nocturia, worry about glucose levels, pain, depressive symptoms, and anxiety, or can result from comorbidities that interfere with sleep.

“It is prudent to ask patients with diabetes about sleep patterns,” said Dr. Reutrakul, and she endorsed the specific question that Dr. Knutson recommended asking patients. Other aspects of sleep quality that could be helpful for a diagnosis include sleep duration, sleep timing, and snoring. “Some physicians ask these questions, but we need to spread awareness,” she added.

Prior to referring patients to a sleep clinic, Dr. Reutrakul suggested that clinicians could also assess possible triggers such as inadequate glucose control, pain, and anxiety, and they could also recommend good sleep hygiene strategies such as what’s recommended by the Sleep Foundation.
 

Sleep disturbances ‘highly prevalent’ among U.K. adults.

The UK Biobank enrolled just over 500,000 people aged 37-73 years during 2006-2010, and 487,728 of these people had data available that allowed their inclusion in the analysis. That group averaged about 57 years of age, 54% were women, 94% were White, and their average body mass index was 27-28 kg/m2.

More than a quarter of these people reported having “usual” sleep disturbances, showing that sleep disturbances are “highly prevalent” among U.K. residents, noted the authors. Just under a quarter of the subjects reported they never or rarely had sleep disturbances, and the remaining half of subjects said they “sometimes” had sleep disturbances.

In addition, 69% reported neither diabetes nor frequent sleep disturbances, 26% had frequent sleep disturbances but no diabetes, 3% had diabetes but not frequent sleep disturbances, and 2% had both diabetes and frequent sleep disturbances.

During the average 8.9-year follow-up, 19,177 people died from any cause (4%), and 3,874 of these deaths involved cardiovascular disease causes. Despite the significant association of diabetes and frequent sleep disturbances with an increased rate of all-cause mortality, the same combination showed no significant link with cardiovascular mortality in the study’s full-adjusted model. This may be because “frequent sleep disturbances can lead to a variety of causes of death,” Dr. Knutson suggested.

The information collected by the UK Biobank did not allow the researchers to distinguish between type 1 and type 2 diabetes.

The findings “suggest that regardless of the cause of sleep disturbance, reporting sleep disturbances on a frequent basis is an important signal of elevated risk of mortality. Such symptoms should therefore be investigated further by physicians, particularly in patients who have also been diagnosed with diabetes,” wrote Dr. Knutson and coauthors. “This is the first study to examine the effect of the combination of insomnia and diabetes on mortality risk.”

But Dr. Knutson highlighted that “sleep problems are important for everyone, not just people with diabetes.

Neither Dr. Knutson and coauthors nor Dr. Reutrakul had no disclosures.

mzoler@mdedge.com

Insulet’s investigational Omnipod 5 automated insulin delivery system improves glycemic control in people with type 1 diabetes aged as young as 2 years, new data suggest.

The Omnipod 5 system combines a tubing-free insulin-filled delivery “Pod” with the Dexcom G6 continuous glucose monitor and an algorithm built into the Pod connecting the two devices via a smartphone app to semiautomate insulin delivery. It is currently under review by the Food and Drug Administration. The company expects to launch it in limited release during the second half of 2021. 

Results from a pivotal trial of the system in children aged 2-5.9 years with type 1 diabetes were presented during the annual scientific sessions of the American Diabetes Association.

Follow-up data at 6 months were also presented for another pivotal study of 112 children aged 6-13.9 years and 129 adults aged 14-70 years. Those primary 3-month data were reported earlier this year at the Endocrine Society’s annual meeting and subsequently published online June 7, 2021, in Diabetes Care. Another study presented at ADA looked at quality of life in children using Omnipod 5 and their caregivers. 

If approved by the FDA, the Omnipod 5 would be the third commercially available automated insulin delivery system – also called hybrid closed-loop or artificial pancreas systems – in the United States. It would be the second approved for children as young as 2 years of age and the first to deliver insulin subcutaneously without tubing.
 

‘No-tubing’ feature will be a draw for parents of young children

Asked to comment, pediatric endocrinologist Laura M. Jacobsen, MD, of the University of Florida, Gainesville, said in an interview: “I think the big advantage for the Omnipod 5 is that [if approved it will be] the only tubeless automated insulin delivery system in the U.S.”

“The automated delivery systems have just been wonderful for helping patients achieve time in range, especially overnight. And the fact that this goes down to such a young age where that can be very difficult is wonderful.”

Another difference between the Omnipod 5 and other systems is the ability to adjust glucose targets (from 110 to 150 mg/dL), although newer versions of the currently available hybrid closed-loop systems are expected to include that feature as well. “They’re all slightly different in the way the algorithms work, but I think the end result is similar,” Dr. Jacobsen said.

But, she said, the no-tubing feature might be particularly helpful for some very active young kids. “A lot of small kids do use the tubed pumps, and you can make it work with a lot of kids, but with some kids it just won’t ... the tubing gets caught. I think this really helps parents make the step. A lot of them don’t want to try the tubing whereas they see the Omnipod and might feel a little more confidence to try a pump.”

Overall, said Dr. Jacobsen, who has no financial disclosures with Insulet, Dexcom, or any of their competitors, “I think any addition to the technology field to improve quality of life for people with type 1 diabetes is important and people need choices.”
 

Pivotal data show benefit in ‘difficult-to-manage’ preschool children

Pivotal 3-month data for the Omnipod 5 in children aged 2-5.9 years with type 1 diabetes were presented on June 26 by pediatric endocrinologist Jennifer Sherr, MD, PhD, Yale University, New Haven, Conn.

“As a pediatric endocrinologist, I can attest to the difficulty of managing this age group, due to grazing eating patterns and erratic physical activity. Oftentimes, care providers may fear hypoglycemia as these youth can not verbalize or self-treat lows,” she remarked.

A total of 80 children were enrolled at 10 institutions across the United Sates. There was a single 14-day standard therapy phase (baseline), followed by 3 months of automated insulin delivery during which the children’s eating and exercise were unrestricted.

At 3 months, average hemoglobin A1c had fallen from 7.4% at baseline to 6.9%, a significant difference (P < .05). The proportions achieving the target A1c of less than 7% were 54% at 3 months versus 31% at baseline. The reduction was even greater among the 25 with baseline A1c of 8% or greater, although it was significant even among the 55 who started with a lower A1c (–1.06 vs. –0.31 percentage points; both P < .05). 

Time in range rose from 57.2% at baseline to 68.1% at 3 months (P < .05).

“These youngsters are spending an average of 2.6 more hours/day in range,” Dr. Sherr commented, noting that the difference became apparent shortly after study start and was maintained during the 3 months.

Dr. Sherr noted that this 10.9% improvement in time in range with Omnipod 5 was similar to improvements in the previously reported pivotal study of older children and adults. Data from that study showed improvement in time in range from a gain of 15.6% for the 6 to 13.9 year olds to 8.0% for those aged 26-49 years. Interestingly, improvements in time in range were seen even in the oldest group, aged 50-70, who increased from an already high baseline of 69.9% to 79.1% with Omnipod 5 after 3 months.

In her current study, in the youngest age group, the improvement in time in range was achieved primarily by a reduction of time above range, from 2.4 fewer hours/day above 180 mg/dL, while time below 70 mg/dL was reduced by 4 minutes/day. Overnight time in range improved by 1.4 hours/night, with most of the improvements in reduction of hyperglycemia.

The proportions meeting the combined goals of less than 4% time below range and greater than 60% time in range rose from 29% to 65%.

There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the 3-month study phase.

Another important related metric, sleep quality for parents/caregivers, also improved. The percentage reporting overall sleep quality of “very good” or “fairly good” increased from 65% at baseline to 90% with Omnipod 5, while “very bad” sleep quality fell from 8.8% to 0%.

All 80 patients completed the study and elected to continue in a 12-month extension phase.
 

Ongoing benefit seen in older children and adults

In a late-breaking poster presented on June 25, Anders L. Carlson, MD, medical director at the International Diabetes Center at Park Nicollet, Minneapolis, presented more follow-up data to the previously reported 3-month pivotal study, including 108 older children and 109 adults from the original study.

A1c remained lower after 6 months than at baseline for both children and adults (P < .001). In the children, A1c levels weren’t significantly different at the end of 6 versus 3 months, while in the adults there was an additional 0.1 percentage point decrease (P < .01).

There was one episode of diabetic ketoacidosis and no severe hypoglycemic episodes in the 3-month extension. “Sustained reduction of A1c indicates the potential long-term benefit of the Omnipod 5 System,” Dr. Carlson and colleagues concluded.
 

Reduced diabetes distress, don’t forget parents’ quality of life

Meanwhile, psychologist Korey K. Hood, PhD, of Stanford (Calif.) University, presented quality of life data at the meeting for 83 children aged 6-11.9 years and 42 teens aged 12-17.9 years using the Omnipod 5 from the larger study population and their parents.

Significant improvements were seen for both the youth and their caregivers in the Problem Areas in Diabetes score, a measure of diabetes-related emotional distress. Changes were less dramatic on the Hypoglycemic Confidence Scale, although improvements were significant for the caregivers of the younger children.

“We know this is a group that is really worried about hypoglycemia across a lot of situations, not just sleep but also school and outside of the home. So, to increase their confidence to this extent I think is a pretty important finding,” Dr. Hood commented.

There were nonsignificant trends in improvement across groups on the Pittsburgh Sleep Quality Index, but overall sleep quality did significantly improve among parents of the younger children. And on the World Health Organization–5 quality of life survey, significant improvements again were seen among the caregivers of young children.

“Reduced diabetes distress and improved quality of life are key benefits of using the Omnipod 5 [automated insulin delivery] system that are complementary to the glycemic benefits achieved,” Dr. Hood said.

Dr. Jacobsen has reported no relevant financial relationships. Dr. Sherr has reported being an adviser for, consultant for, and/or grant recipient from Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, Eli Lilly, Lexicon, Sanofi, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hood has reported being a consultant for Cecelia Health, Havas, and Cercacor.

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

Insulet’s investigational Omnipod 5 automated insulin delivery system improves glycemic control in people with type 1 diabetes aged as young as 2 years, new data suggest.

The Omnipod 5 system combines a tubing-free insulin-filled delivery “Pod” with the Dexcom G6 continuous glucose monitor and an algorithm built into the Pod connecting the two devices via a smartphone app to semiautomate insulin delivery. It is currently under review by the Food and Drug Administration. The company expects to launch it in limited release during the second half of 2021. 

Results from a pivotal trial of the system in children aged 2-5.9 years with type 1 diabetes were presented during the annual scientific sessions of the American Diabetes Association.

Follow-up data at 6 months were also presented for another pivotal study of 112 children aged 6-13.9 years and 129 adults aged 14-70 years. Those primary 3-month data were reported earlier this year at the Endocrine Society’s annual meeting and subsequently published online June 7, 2021, in Diabetes Care. Another study presented at ADA looked at quality of life in children using Omnipod 5 and their caregivers. 

If approved by the FDA, the Omnipod 5 would be the third commercially available automated insulin delivery system – also called hybrid closed-loop or artificial pancreas systems – in the United States. It would be the second approved for children as young as 2 years of age and the first to deliver insulin subcutaneously without tubing.
 

‘No-tubing’ feature will be a draw for parents of young children

Asked to comment, pediatric endocrinologist Laura M. Jacobsen, MD, of the University of Florida, Gainesville, said in an interview: “I think the big advantage for the Omnipod 5 is that [if approved it will be] the only tubeless automated insulin delivery system in the U.S.”

“The automated delivery systems have just been wonderful for helping patients achieve time in range, especially overnight. And the fact that this goes down to such a young age where that can be very difficult is wonderful.”

Another difference between the Omnipod 5 and other systems is the ability to adjust glucose targets (from 110 to 150 mg/dL), although newer versions of the currently available hybrid closed-loop systems are expected to include that feature as well. “They’re all slightly different in the way the algorithms work, but I think the end result is similar,” Dr. Jacobsen said.

But, she said, the no-tubing feature might be particularly helpful for some very active young kids. “A lot of small kids do use the tubed pumps, and you can make it work with a lot of kids, but with some kids it just won’t ... the tubing gets caught. I think this really helps parents make the step. A lot of them don’t want to try the tubing whereas they see the Omnipod and might feel a little more confidence to try a pump.”

Overall, said Dr. Jacobsen, who has no financial disclosures with Insulet, Dexcom, or any of their competitors, “I think any addition to the technology field to improve quality of life for people with type 1 diabetes is important and people need choices.”
 

Pivotal data show benefit in ‘difficult-to-manage’ preschool children

Pivotal 3-month data for the Omnipod 5 in children aged 2-5.9 years with type 1 diabetes were presented on June 26 by pediatric endocrinologist Jennifer Sherr, MD, PhD, Yale University, New Haven, Conn.

“As a pediatric endocrinologist, I can attest to the difficulty of managing this age group, due to grazing eating patterns and erratic physical activity. Oftentimes, care providers may fear hypoglycemia as these youth can not verbalize or self-treat lows,” she remarked.

A total of 80 children were enrolled at 10 institutions across the United Sates. There was a single 14-day standard therapy phase (baseline), followed by 3 months of automated insulin delivery during which the children’s eating and exercise were unrestricted.

At 3 months, average hemoglobin A1c had fallen from 7.4% at baseline to 6.9%, a significant difference (P < .05). The proportions achieving the target A1c of less than 7% were 54% at 3 months versus 31% at baseline. The reduction was even greater among the 25 with baseline A1c of 8% or greater, although it was significant even among the 55 who started with a lower A1c (–1.06 vs. –0.31 percentage points; both P < .05). 

Time in range rose from 57.2% at baseline to 68.1% at 3 months (P < .05).

“These youngsters are spending an average of 2.6 more hours/day in range,” Dr. Sherr commented, noting that the difference became apparent shortly after study start and was maintained during the 3 months.

Dr. Sherr noted that this 10.9% improvement in time in range with Omnipod 5 was similar to improvements in the previously reported pivotal study of older children and adults. Data from that study showed improvement in time in range from a gain of 15.6% for the 6 to 13.9 year olds to 8.0% for those aged 26-49 years. Interestingly, improvements in time in range were seen even in the oldest group, aged 50-70, who increased from an already high baseline of 69.9% to 79.1% with Omnipod 5 after 3 months.

In her current study, in the youngest age group, the improvement in time in range was achieved primarily by a reduction of time above range, from 2.4 fewer hours/day above 180 mg/dL, while time below 70 mg/dL was reduced by 4 minutes/day. Overnight time in range improved by 1.4 hours/night, with most of the improvements in reduction of hyperglycemia.

The proportions meeting the combined goals of less than 4% time below range and greater than 60% time in range rose from 29% to 65%.

There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the 3-month study phase.

Another important related metric, sleep quality for parents/caregivers, also improved. The percentage reporting overall sleep quality of “very good” or “fairly good” increased from 65% at baseline to 90% with Omnipod 5, while “very bad” sleep quality fell from 8.8% to 0%.

All 80 patients completed the study and elected to continue in a 12-month extension phase.
 

Ongoing benefit seen in older children and adults

In a late-breaking poster presented on June 25, Anders L. Carlson, MD, medical director at the International Diabetes Center at Park Nicollet, Minneapolis, presented more follow-up data to the previously reported 3-month pivotal study, including 108 older children and 109 adults from the original study.

A1c remained lower after 6 months than at baseline for both children and adults (P < .001). In the children, A1c levels weren’t significantly different at the end of 6 versus 3 months, while in the adults there was an additional 0.1 percentage point decrease (P < .01).

There was one episode of diabetic ketoacidosis and no severe hypoglycemic episodes in the 3-month extension. “Sustained reduction of A1c indicates the potential long-term benefit of the Omnipod 5 System,” Dr. Carlson and colleagues concluded.
 

Reduced diabetes distress, don’t forget parents’ quality of life

Meanwhile, psychologist Korey K. Hood, PhD, of Stanford (Calif.) University, presented quality of life data at the meeting for 83 children aged 6-11.9 years and 42 teens aged 12-17.9 years using the Omnipod 5 from the larger study population and their parents.

Significant improvements were seen for both the youth and their caregivers in the Problem Areas in Diabetes score, a measure of diabetes-related emotional distress. Changes were less dramatic on the Hypoglycemic Confidence Scale, although improvements were significant for the caregivers of the younger children.

“We know this is a group that is really worried about hypoglycemia across a lot of situations, not just sleep but also school and outside of the home. So, to increase their confidence to this extent I think is a pretty important finding,” Dr. Hood commented.

There were nonsignificant trends in improvement across groups on the Pittsburgh Sleep Quality Index, but overall sleep quality did significantly improve among parents of the younger children. And on the World Health Organization–5 quality of life survey, significant improvements again were seen among the caregivers of young children.

“Reduced diabetes distress and improved quality of life are key benefits of using the Omnipod 5 [automated insulin delivery] system that are complementary to the glycemic benefits achieved,” Dr. Hood said.

Dr. Jacobsen has reported no relevant financial relationships. Dr. Sherr has reported being an adviser for, consultant for, and/or grant recipient from Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, Eli Lilly, Lexicon, Sanofi, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hood has reported being a consultant for Cecelia Health, Havas, and Cercacor.

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

Insulet’s investigational Omnipod 5 automated insulin delivery system improves glycemic control in people with type 1 diabetes aged as young as 2 years, new data suggest.

The Omnipod 5 system combines a tubing-free insulin-filled delivery “Pod” with the Dexcom G6 continuous glucose monitor and an algorithm built into the Pod connecting the two devices via a smartphone app to semiautomate insulin delivery. It is currently under review by the Food and Drug Administration. The company expects to launch it in limited release during the second half of 2021. 

Results from a pivotal trial of the system in children aged 2-5.9 years with type 1 diabetes were presented during the annual scientific sessions of the American Diabetes Association.

Follow-up data at 6 months were also presented for another pivotal study of 112 children aged 6-13.9 years and 129 adults aged 14-70 years. Those primary 3-month data were reported earlier this year at the Endocrine Society’s annual meeting and subsequently published online June 7, 2021, in Diabetes Care. Another study presented at ADA looked at quality of life in children using Omnipod 5 and their caregivers. 

If approved by the FDA, the Omnipod 5 would be the third commercially available automated insulin delivery system – also called hybrid closed-loop or artificial pancreas systems – in the United States. It would be the second approved for children as young as 2 years of age and the first to deliver insulin subcutaneously without tubing.
 

‘No-tubing’ feature will be a draw for parents of young children

Asked to comment, pediatric endocrinologist Laura M. Jacobsen, MD, of the University of Florida, Gainesville, said in an interview: “I think the big advantage for the Omnipod 5 is that [if approved it will be] the only tubeless automated insulin delivery system in the U.S.”

“The automated delivery systems have just been wonderful for helping patients achieve time in range, especially overnight. And the fact that this goes down to such a young age where that can be very difficult is wonderful.”

Another difference between the Omnipod 5 and other systems is the ability to adjust glucose targets (from 110 to 150 mg/dL), although newer versions of the currently available hybrid closed-loop systems are expected to include that feature as well. “They’re all slightly different in the way the algorithms work, but I think the end result is similar,” Dr. Jacobsen said.

But, she said, the no-tubing feature might be particularly helpful for some very active young kids. “A lot of small kids do use the tubed pumps, and you can make it work with a lot of kids, but with some kids it just won’t ... the tubing gets caught. I think this really helps parents make the step. A lot of them don’t want to try the tubing whereas they see the Omnipod and might feel a little more confidence to try a pump.”

Overall, said Dr. Jacobsen, who has no financial disclosures with Insulet, Dexcom, or any of their competitors, “I think any addition to the technology field to improve quality of life for people with type 1 diabetes is important and people need choices.”
 

Pivotal data show benefit in ‘difficult-to-manage’ preschool children

Pivotal 3-month data for the Omnipod 5 in children aged 2-5.9 years with type 1 diabetes were presented on June 26 by pediatric endocrinologist Jennifer Sherr, MD, PhD, Yale University, New Haven, Conn.

“As a pediatric endocrinologist, I can attest to the difficulty of managing this age group, due to grazing eating patterns and erratic physical activity. Oftentimes, care providers may fear hypoglycemia as these youth can not verbalize or self-treat lows,” she remarked.

A total of 80 children were enrolled at 10 institutions across the United Sates. There was a single 14-day standard therapy phase (baseline), followed by 3 months of automated insulin delivery during which the children’s eating and exercise were unrestricted.

At 3 months, average hemoglobin A1c had fallen from 7.4% at baseline to 6.9%, a significant difference (P < .05). The proportions achieving the target A1c of less than 7% were 54% at 3 months versus 31% at baseline. The reduction was even greater among the 25 with baseline A1c of 8% or greater, although it was significant even among the 55 who started with a lower A1c (–1.06 vs. –0.31 percentage points; both P < .05). 

Time in range rose from 57.2% at baseline to 68.1% at 3 months (P < .05).

“These youngsters are spending an average of 2.6 more hours/day in range,” Dr. Sherr commented, noting that the difference became apparent shortly after study start and was maintained during the 3 months.

Dr. Sherr noted that this 10.9% improvement in time in range with Omnipod 5 was similar to improvements in the previously reported pivotal study of older children and adults. Data from that study showed improvement in time in range from a gain of 15.6% for the 6 to 13.9 year olds to 8.0% for those aged 26-49 years. Interestingly, improvements in time in range were seen even in the oldest group, aged 50-70, who increased from an already high baseline of 69.9% to 79.1% with Omnipod 5 after 3 months.

In her current study, in the youngest age group, the improvement in time in range was achieved primarily by a reduction of time above range, from 2.4 fewer hours/day above 180 mg/dL, while time below 70 mg/dL was reduced by 4 minutes/day. Overnight time in range improved by 1.4 hours/night, with most of the improvements in reduction of hyperglycemia.

The proportions meeting the combined goals of less than 4% time below range and greater than 60% time in range rose from 29% to 65%.

There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the 3-month study phase.

Another important related metric, sleep quality for parents/caregivers, also improved. The percentage reporting overall sleep quality of “very good” or “fairly good” increased from 65% at baseline to 90% with Omnipod 5, while “very bad” sleep quality fell from 8.8% to 0%.

All 80 patients completed the study and elected to continue in a 12-month extension phase.
 

Ongoing benefit seen in older children and adults

In a late-breaking poster presented on June 25, Anders L. Carlson, MD, medical director at the International Diabetes Center at Park Nicollet, Minneapolis, presented more follow-up data to the previously reported 3-month pivotal study, including 108 older children and 109 adults from the original study.

A1c remained lower after 6 months than at baseline for both children and adults (P < .001). In the children, A1c levels weren’t significantly different at the end of 6 versus 3 months, while in the adults there was an additional 0.1 percentage point decrease (P < .01).

There was one episode of diabetic ketoacidosis and no severe hypoglycemic episodes in the 3-month extension. “Sustained reduction of A1c indicates the potential long-term benefit of the Omnipod 5 System,” Dr. Carlson and colleagues concluded.
 

Reduced diabetes distress, don’t forget parents’ quality of life

Meanwhile, psychologist Korey K. Hood, PhD, of Stanford (Calif.) University, presented quality of life data at the meeting for 83 children aged 6-11.9 years and 42 teens aged 12-17.9 years using the Omnipod 5 from the larger study population and their parents.

Significant improvements were seen for both the youth and their caregivers in the Problem Areas in Diabetes score, a measure of diabetes-related emotional distress. Changes were less dramatic on the Hypoglycemic Confidence Scale, although improvements were significant for the caregivers of the younger children.

“We know this is a group that is really worried about hypoglycemia across a lot of situations, not just sleep but also school and outside of the home. So, to increase their confidence to this extent I think is a pretty important finding,” Dr. Hood commented.

There were nonsignificant trends in improvement across groups on the Pittsburgh Sleep Quality Index, but overall sleep quality did significantly improve among parents of the younger children. And on the World Health Organization–5 quality of life survey, significant improvements again were seen among the caregivers of young children.

“Reduced diabetes distress and improved quality of life are key benefits of using the Omnipod 5 [automated insulin delivery] system that are complementary to the glycemic benefits achieved,” Dr. Hood said.

Dr. Jacobsen has reported no relevant financial relationships. Dr. Sherr has reported being an adviser for, consultant for, and/or grant recipient from Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, Eli Lilly, Lexicon, Sanofi, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hood has reported being a consultant for Cecelia Health, Havas, and Cercacor.

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

For racial or ethnic minority youths with type 1 diabetes, participating in an interventional program improves access to care, new research shows.

Youth categorized as Black, Indigenous, and other people of color (BIPOC) had significantly improved outpatient attendance during and after participating in Novel Interventions in Children’s Healthcare (NICH), a systems intervention for children with chronic health conditions and their families.

By comparison, no improvements in care access were observed among BIPOC children who were not able to access the program because of insurance or other reasons, David V. Wagner, PhD, Associate Professor and NICH research director at Oregon Health & Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.

The findings demonstrate a need for intensive, home-based services that aim to correct health inequities, said Dr. Wagner, who presented the findings along with Winniebhelle Cadiz, a scholar in the BUILD EXITO undergraduate research training program at Portland (Ore.) State University.

The NICH program hinges on trained interventionists who visit families at home, attend clinic visits, and work with schools and other contacts to help solve problems that keep children from following medical instructions, according to a program description.

“Families report having somebody by their side to help them navigate the system, address the transportation difficulties experienced, and help them and build that relationship with their health care provider seems to be hugely influential in terms of helping them navigate and access care,” Dr. Wagner said in a presentation of the study.
 

A NICH for youths with chronic health conditions

The NICH program differs from some other programs that have been developed in an attempt to improve health outcomes among youths in the community, according to Dr. Wagner.

“Many of the programs that exist out there are often piloted on, and seemingly built for, those who have more resources,” he said in his presentation. “Those who are in greatest need often have difficulty accessing and responding to the services.”

NICH doesn’t take the place of existing services, but is “an addition to the continuum of care” for youths and families who are struggling because of lack of resources or marginalization in the health care system, Dr. Wagner said.

While NICH is not specific to any one chronic health condition, several previous investigations have specifically looked at the impact of the NICH program on access to care in youths with type 1 diabetes.

Youths participating in the program for a year had fewer ED visits, including fewer visits with diabetic ketoacidosis (DKA), as well as fewer and shorter admissions as compared with the year prior to participating in the program, Dr. Wagner said.

In another study, youths had fewer admissions for diabetes or DKA and less frequent pediatric ICU contact during the NICH program, as compared with before the program.

Another study showed that, while NICH had no impact overall on access to care among youths with type 1 diabetes, BIPOC youths had an improvement in the mean number of outpatient visits as compared with preprogram levels. However, because none of those studies included a control group, Dr. Wagner said, it remained unclear whether this systems intervention might improve outpatient access among youths with type 1 diabetes as compared with those who did not participate.
 

Intervention linked to increased BIPOC care access

The latest study includes 144 youths with type 1 diabetes referred for the program. The mean age was 13.7 years, 58% were female, and 81% were non-Hispanic White. While 51 youths were able to participate in NICH, the remaining 93 were not served by the program because of insurance denial or nonresponse, according to investigators.

While participation in the program made no difference in access to care overall, results of this study suggest NICH reduced access disparities among BIPOC youths, the investigators said.

Those BIPOC youth, 28 in total, had significantly worse access to care prior to referral. However, BIPOC youth participation in NICH was associated with improved attendance at endocrinology appointments and outpatient attendance overall.

A mean change of 1.9 more appointments per year was seen among BIPOC youth who participated in NICH, compared with a mean decrease of 0.5 appointments per year among BIPOC youth not served by the program (P = .03), according to the study abstract.

Prior to NICH participation, outpatient attendance among BIPOC youths was about 2.5 visits per year, data presented by the investigators show.
 

Systemic changes needed

This study is representative of systemic changes that are needed to improve access to quality care for BIPOC youth, according Cynthia E. Muñoz, PhD, MPH, ADA’s president of health care and education.

“We know that there are increased risks for poor health outcomes for these children and youths, and we know that there is a risk for mental health and psychosocial challenges for youth from these communities,” said Dr. Muñoz, a bilingual licensed psychologist and assistant professor of clinical pediatrics at the University of Southern California, Los Angeles.

In his presentation, Dr. Wagner said lumping racial and ethnic minority participants under a single BIPOC header probably wasn’t ideal because of the diversity and differences among racial and ethnic minorities. However, it was necessary in this particular study because of limited sample size.

Dr. Wagner and coauthors disclosed no conflicts of interest related to the research, which was supported by the Leona M. and Harry B. Helmsley Charitable Trust.

For racial or ethnic minority youths with type 1 diabetes, participating in an interventional program improves access to care, new research shows.

Youth categorized as Black, Indigenous, and other people of color (BIPOC) had significantly improved outpatient attendance during and after participating in Novel Interventions in Children’s Healthcare (NICH), a systems intervention for children with chronic health conditions and their families.

By comparison, no improvements in care access were observed among BIPOC children who were not able to access the program because of insurance or other reasons, David V. Wagner, PhD, Associate Professor and NICH research director at Oregon Health & Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.

The findings demonstrate a need for intensive, home-based services that aim to correct health inequities, said Dr. Wagner, who presented the findings along with Winniebhelle Cadiz, a scholar in the BUILD EXITO undergraduate research training program at Portland (Ore.) State University.

The NICH program hinges on trained interventionists who visit families at home, attend clinic visits, and work with schools and other contacts to help solve problems that keep children from following medical instructions, according to a program description.

“Families report having somebody by their side to help them navigate the system, address the transportation difficulties experienced, and help them and build that relationship with their health care provider seems to be hugely influential in terms of helping them navigate and access care,” Dr. Wagner said in a presentation of the study.
 

A NICH for youths with chronic health conditions

The NICH program differs from some other programs that have been developed in an attempt to improve health outcomes among youths in the community, according to Dr. Wagner.

“Many of the programs that exist out there are often piloted on, and seemingly built for, those who have more resources,” he said in his presentation. “Those who are in greatest need often have difficulty accessing and responding to the services.”

NICH doesn’t take the place of existing services, but is “an addition to the continuum of care” for youths and families who are struggling because of lack of resources or marginalization in the health care system, Dr. Wagner said.

While NICH is not specific to any one chronic health condition, several previous investigations have specifically looked at the impact of the NICH program on access to care in youths with type 1 diabetes.

Youths participating in the program for a year had fewer ED visits, including fewer visits with diabetic ketoacidosis (DKA), as well as fewer and shorter admissions as compared with the year prior to participating in the program, Dr. Wagner said.

In another study, youths had fewer admissions for diabetes or DKA and less frequent pediatric ICU contact during the NICH program, as compared with before the program.

Another study showed that, while NICH had no impact overall on access to care among youths with type 1 diabetes, BIPOC youths had an improvement in the mean number of outpatient visits as compared with preprogram levels. However, because none of those studies included a control group, Dr. Wagner said, it remained unclear whether this systems intervention might improve outpatient access among youths with type 1 diabetes as compared with those who did not participate.
 

Intervention linked to increased BIPOC care access

The latest study includes 144 youths with type 1 diabetes referred for the program. The mean age was 13.7 years, 58% were female, and 81% were non-Hispanic White. While 51 youths were able to participate in NICH, the remaining 93 were not served by the program because of insurance denial or nonresponse, according to investigators.

While participation in the program made no difference in access to care overall, results of this study suggest NICH reduced access disparities among BIPOC youths, the investigators said.

Those BIPOC youth, 28 in total, had significantly worse access to care prior to referral. However, BIPOC youth participation in NICH was associated with improved attendance at endocrinology appointments and outpatient attendance overall.

A mean change of 1.9 more appointments per year was seen among BIPOC youth who participated in NICH, compared with a mean decrease of 0.5 appointments per year among BIPOC youth not served by the program (P = .03), according to the study abstract.

Prior to NICH participation, outpatient attendance among BIPOC youths was about 2.5 visits per year, data presented by the investigators show.
 

Systemic changes needed

This study is representative of systemic changes that are needed to improve access to quality care for BIPOC youth, according Cynthia E. Muñoz, PhD, MPH, ADA’s president of health care and education.

“We know that there are increased risks for poor health outcomes for these children and youths, and we know that there is a risk for mental health and psychosocial challenges for youth from these communities,” said Dr. Muñoz, a bilingual licensed psychologist and assistant professor of clinical pediatrics at the University of Southern California, Los Angeles.

In his presentation, Dr. Wagner said lumping racial and ethnic minority participants under a single BIPOC header probably wasn’t ideal because of the diversity and differences among racial and ethnic minorities. However, it was necessary in this particular study because of limited sample size.

Dr. Wagner and coauthors disclosed no conflicts of interest related to the research, which was supported by the Leona M. and Harry B. Helmsley Charitable Trust.

For racial or ethnic minority youths with type 1 diabetes, participating in an interventional program improves access to care, new research shows.

Youth categorized as Black, Indigenous, and other people of color (BIPOC) had significantly improved outpatient attendance during and after participating in Novel Interventions in Children’s Healthcare (NICH), a systems intervention for children with chronic health conditions and their families.

By comparison, no improvements in care access were observed among BIPOC children who were not able to access the program because of insurance or other reasons, David V. Wagner, PhD, Associate Professor and NICH research director at Oregon Health & Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.

The findings demonstrate a need for intensive, home-based services that aim to correct health inequities, said Dr. Wagner, who presented the findings along with Winniebhelle Cadiz, a scholar in the BUILD EXITO undergraduate research training program at Portland (Ore.) State University.

The NICH program hinges on trained interventionists who visit families at home, attend clinic visits, and work with schools and other contacts to help solve problems that keep children from following medical instructions, according to a program description.

“Families report having somebody by their side to help them navigate the system, address the transportation difficulties experienced, and help them and build that relationship with their health care provider seems to be hugely influential in terms of helping them navigate and access care,” Dr. Wagner said in a presentation of the study.
 

A NICH for youths with chronic health conditions

The NICH program differs from some other programs that have been developed in an attempt to improve health outcomes among youths in the community, according to Dr. Wagner.

“Many of the programs that exist out there are often piloted on, and seemingly built for, those who have more resources,” he said in his presentation. “Those who are in greatest need often have difficulty accessing and responding to the services.”

NICH doesn’t take the place of existing services, but is “an addition to the continuum of care” for youths and families who are struggling because of lack of resources or marginalization in the health care system, Dr. Wagner said.

While NICH is not specific to any one chronic health condition, several previous investigations have specifically looked at the impact of the NICH program on access to care in youths with type 1 diabetes.

Youths participating in the program for a year had fewer ED visits, including fewer visits with diabetic ketoacidosis (DKA), as well as fewer and shorter admissions as compared with the year prior to participating in the program, Dr. Wagner said.

In another study, youths had fewer admissions for diabetes or DKA and less frequent pediatric ICU contact during the NICH program, as compared with before the program.

Another study showed that, while NICH had no impact overall on access to care among youths with type 1 diabetes, BIPOC youths had an improvement in the mean number of outpatient visits as compared with preprogram levels. However, because none of those studies included a control group, Dr. Wagner said, it remained unclear whether this systems intervention might improve outpatient access among youths with type 1 diabetes as compared with those who did not participate.
 

Intervention linked to increased BIPOC care access

The latest study includes 144 youths with type 1 diabetes referred for the program. The mean age was 13.7 years, 58% were female, and 81% were non-Hispanic White. While 51 youths were able to participate in NICH, the remaining 93 were not served by the program because of insurance denial or nonresponse, according to investigators.

While participation in the program made no difference in access to care overall, results of this study suggest NICH reduced access disparities among BIPOC youths, the investigators said.

Those BIPOC youth, 28 in total, had significantly worse access to care prior to referral. However, BIPOC youth participation in NICH was associated with improved attendance at endocrinology appointments and outpatient attendance overall.

A mean change of 1.9 more appointments per year was seen among BIPOC youth who participated in NICH, compared with a mean decrease of 0.5 appointments per year among BIPOC youth not served by the program (P = .03), according to the study abstract.

Prior to NICH participation, outpatient attendance among BIPOC youths was about 2.5 visits per year, data presented by the investigators show.
 

Systemic changes needed

This study is representative of systemic changes that are needed to improve access to quality care for BIPOC youth, according Cynthia E. Muñoz, PhD, MPH, ADA’s president of health care and education.

“We know that there are increased risks for poor health outcomes for these children and youths, and we know that there is a risk for mental health and psychosocial challenges for youth from these communities,” said Dr. Muñoz, a bilingual licensed psychologist and assistant professor of clinical pediatrics at the University of Southern California, Los Angeles.

In his presentation, Dr. Wagner said lumping racial and ethnic minority participants under a single BIPOC header probably wasn’t ideal because of the diversity and differences among racial and ethnic minorities. However, it was necessary in this particular study because of limited sample size.

Dr. Wagner and coauthors disclosed no conflicts of interest related to the research, which was supported by the Leona M. and Harry B. Helmsley Charitable Trust.

The risk of amputations in persons with type 1 diabetes in Sweden has decreased over time, suggesting an improvement in the course of disease for these individuals, according to a national registry analysis.

Balkonsky/Thinkstock

The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.

Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.

“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
 

Drilling down on amputation risk in type 1 diabetes

Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).

“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.

Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.

Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
 

Trends over time

In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.

The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.

The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.

Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.

Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.

Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
 

U.S. amputations on the rise overall

While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.

“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”

Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.

To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.

In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.

Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.

The risk of amputations in persons with type 1 diabetes in Sweden has decreased over time, suggesting an improvement in the course of disease for these individuals, according to a national registry analysis.

Balkonsky/Thinkstock

The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.

Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.

“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
 

Drilling down on amputation risk in type 1 diabetes

Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).

“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.

Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.

Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
 

Trends over time

In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.

The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.

The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.

Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.

Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.

Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
 

U.S. amputations on the rise overall

While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.

“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”

Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.

To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.

In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.

Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.

The risk of amputations in persons with type 1 diabetes in Sweden has decreased over time, suggesting an improvement in the course of disease for these individuals, according to a national registry analysis.

Balkonsky/Thinkstock

The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.

Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.

“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
 

Drilling down on amputation risk in type 1 diabetes

Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).

“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.

Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.

Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
 

Trends over time

In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.

The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.

The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.

Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.

Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.

Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
 

U.S. amputations on the rise overall

While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.

“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”

Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.

To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.

In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.

Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.

Accumulating evidence shows that for many patients with type 2 diabetes, a bigger dose of the glucagonlike peptide–1 receptor agonist semaglutide is better if the goal is a larger decrease in hemoglobin A1c and weight.

Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.

“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.

Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).

In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.

Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.

A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
 

Gradual up-titration aids tolerance

“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”

Courtesy Joslin Diabetes Center

A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.

The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.

Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).

“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
 

Several doses to choose from

SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.

The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).

Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.

In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.

SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.

mzoler@mdedge.com

Accumulating evidence shows that for many patients with type 2 diabetes, a bigger dose of the glucagonlike peptide–1 receptor agonist semaglutide is better if the goal is a larger decrease in hemoglobin A1c and weight.

Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.

“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.

Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).

In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.

Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.

A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
 

Gradual up-titration aids tolerance

“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”

Courtesy Joslin Diabetes Center

A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.

The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.

Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).

“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
 

Several doses to choose from

SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.

The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).

Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.

In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.

SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.

mzoler@mdedge.com

Accumulating evidence shows that for many patients with type 2 diabetes, a bigger dose of the glucagonlike peptide–1 receptor agonist semaglutide is better if the goal is a larger decrease in hemoglobin A1c and weight.

Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.

“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.

Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).

In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.

Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.

A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
 

Gradual up-titration aids tolerance

“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”

Courtesy Joslin Diabetes Center

A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.

The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.

Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).

“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
 

Several doses to choose from

SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.

The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).

Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.

In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.

SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.

mzoler@mdedge.com

The incidence of type 2 diabetes in children appears to have doubled during the COVID-19 pandemic, data from two new U.S. studies suggest, with the lead investigator of one saying she was “surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”

Anetta_R/Thinkstock

Findings from the two separate retrospective chart reviews – one conducted in Washington, D.C., and the other in Baton Rouge, La. – were presented June 25 at the annual scientific sessions of the American Diabetes Association.

Although the two studies differed somewhat in the clinical parameters examined, both revealed a similar doubling of the rates of hospitalizations for type 2 diabetes among youth during 2020, compared with the same time period in 2019, as well as greater severity of metabolic disturbance.

And, as has been previously described with type 2 diabetes in youth, African American ethnicity predominated in both cohorts.

“Although we could not assess the cause of the increases in type 2 diabetes from our data, these disparities suggest that indirect effects of social distancing measures, including school closure and unemployment, are placing undue burden on underserved communities. Decreases in well-child care and fears of seeking medical care during the pandemic may have also contributed,” lead investigator of one of the studies, pediatric endocrinologist Brynn E. Marks, MD, Children’s National Hospital, Washington, said in an interview.
 

More hospitalizations, racial disparities aggravated by COVID-19

Lead author of the other study, Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, said in an interview: “Since the pandemic, our data suggest that more children may be diagnosed with type 2 diabetes and may require hospitalization when they are diagnosed. Looking at both datasets, there appears to be a racial disparity in type 2 diabetes diagnoses that has only been exacerbated by the COVID-19 pandemic.”

Of concern, Dr. Hsia said, “The incidence rate of type 2 diabetes in children was already on the rise before the pandemic. While there may be a brief leveling off now that children are getting regular health care and going back to school in person, I believe these rates will continue to rise especially in light of the childhood obesity rates not improving.”

Their dataset captured all youth who were newly diagnosed with type 2 diabetes during the first full year of the COVID-19 pandemic, from March 11, 2020, to March 10, 2021, and compared those data with the time period from March 11, 2019, to March 10, 2020.

During the pandemic, the number of cases of type 2 diabetes increased by 182%, from 50 in 2019 to 141 in 2020. The average age at diagnosis was about 14 years in both time periods.

In the prepandemic period, 18 (36%) diagnosed with type 2 diabetes required inpatient admission, compared with 85 (60.3%) during the pandemic. At Children’s National, youth with suspected new-onset type 2 diabetes aren’t typically hospitalized unless they have severe hyperglycemia, ketosis, or are unable to schedule urgent outpatient follow-up, Dr. Marks noted.

The proportions of youth with new-onset type 2 diabetes who presented in diabetic ketoacidosis (DKA) rose from 2 (4%) prepandemic to 33 (23.4%) during the pandemic. Presentation with hyperosmolar DKA rose from 0 to 13 (9.2%).

However, during the pandemic only five youth were actively infected with SARS-CoV-2 at the time of type 2 diabetes diagnosis among the 90 tested.

Dr. Marks said: “We believe the increase in inpatient admissions was due to more severe presentation during the pandemic. ...We were surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
 

Shift in diagnoses to type 2 diabetes

The pandemic also appears to have shifted the proportion of youth diagnosed with type 2 diabetes, compared with type 1 diabetes. Whereas 24% of youth with new-onset diabetes prepandemic had type 2 diabetes and the rest had type 1 diabetes, during pandemic the proportion with type 2 diabetes rose to 44%.

“Rates of type 2 diabetes rose steadily at a rate of 1.45 cases per month throughout the course of the pandemic, suggesting a cumulative effect of the indirect effects of social distancing measures,” Dr. Marks said.

Furthermore, she added, whereas 60% of youth diagnosed with type 2 diabetes before the pandemic were female, the rate fell to 40% during the pandemic. This trend might be because of activity levels in that, while male adolescents are typically more active, rates of exercise fell in both sexes during the pandemic but declined more sharply in males such that activity levels between the sexes became equal.  

Although type 2 diabetes in youth has always been more common in ethnic minorities, the pandemic appears to have exacerbated these disparities.

While 58% of youth diagnosed with type 2 diabetes prepandemic identified as non-Hispanic Black, that proportion rose to 76.7% during the pandemic. Among Black youth with new-onset type 2 diabetes, 31 of 33 presented in DKA, and 12 of the 13 who presented in hyperosmolar DKA during the pandemic were Black.

“Strategies to promote health equity and address the undue burden of the COVID-19 pandemic on underserved communities must be developed to avoid worsening disparities and long-term health outcomes,” Dr. Marks said.
 

‘A microcosm’: Similar findings in a smaller population

Dr. Hsia and colleagues looked at a smaller number of patients in a shorter time period. In March–December 2019, the hospitalization rate for new-onset type 2 diabetes was 0.27% (8 out of 2,964 hospitalizations), compared with 0.62% (17 out of 2,729 hospitalizations) during the same period in 2020 (P < .048) – also more than a doubling. Age at admission, sex, and body mass index didn’t differ between the two groups.

Criteria for DKA were met by three children in 2019 versus eight in 2020, and hyperosmolar hyperglycemic syndrome in zero versus two, respectively. Mean hemoglobin A1c on admission was 12.4% in 2019 versus 13.1% in 2020 (P = .59), and mean serum glucose was 441 mg/dL versus 669 mg/dL (P = .14), respectively. Serum osmolality on admission was 314 mmol/kg in 2019 versus 335 mmol/kg in 2020 (P = .19).

“Clinically speaking the differences in the lab values were significant, but we did not have enough numbers ... to see a statistically significant difference. I think by looking at more centers, our site likely represents a microcosm of what is happening across the country,” Dr. Hsia said.

In 2019, 7 of the 8 children were African American, as were 16 of the 17 children in 2020. The other single child in each group was White.

Dr. Hsia said: “Larger studies that include more patients are needed to confirm our initial findings. More research is needed to understand why this increasing trend of type 2 diabetes diagnoses in children may be occurring [and] to better understand how stay-at-home orders and other restrictions due to COVID-19 have worsened risk factors for type 2 diabetes.”

“These include decreased physical activity, more screen time, disturbed sleep, and increased intake of processed foods, which can all lead to weight gain,” he concluded.

Dr. Marks reported receiving research support from Tandem, Dexcom, and the Cystic Fibrosis Foundation. Dr. Hsia reported no relevant financial relationships.

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

The incidence of type 2 diabetes in children appears to have doubled during the COVID-19 pandemic, data from two new U.S. studies suggest, with the lead investigator of one saying she was “surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”

Anetta_R/Thinkstock

Findings from the two separate retrospective chart reviews – one conducted in Washington, D.C., and the other in Baton Rouge, La. – were presented June 25 at the annual scientific sessions of the American Diabetes Association.

Although the two studies differed somewhat in the clinical parameters examined, both revealed a similar doubling of the rates of hospitalizations for type 2 diabetes among youth during 2020, compared with the same time period in 2019, as well as greater severity of metabolic disturbance.

And, as has been previously described with type 2 diabetes in youth, African American ethnicity predominated in both cohorts.

“Although we could not assess the cause of the increases in type 2 diabetes from our data, these disparities suggest that indirect effects of social distancing measures, including school closure and unemployment, are placing undue burden on underserved communities. Decreases in well-child care and fears of seeking medical care during the pandemic may have also contributed,” lead investigator of one of the studies, pediatric endocrinologist Brynn E. Marks, MD, Children’s National Hospital, Washington, said in an interview.
 

More hospitalizations, racial disparities aggravated by COVID-19

Lead author of the other study, Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, said in an interview: “Since the pandemic, our data suggest that more children may be diagnosed with type 2 diabetes and may require hospitalization when they are diagnosed. Looking at both datasets, there appears to be a racial disparity in type 2 diabetes diagnoses that has only been exacerbated by the COVID-19 pandemic.”

Of concern, Dr. Hsia said, “The incidence rate of type 2 diabetes in children was already on the rise before the pandemic. While there may be a brief leveling off now that children are getting regular health care and going back to school in person, I believe these rates will continue to rise especially in light of the childhood obesity rates not improving.”

Their dataset captured all youth who were newly diagnosed with type 2 diabetes during the first full year of the COVID-19 pandemic, from March 11, 2020, to March 10, 2021, and compared those data with the time period from March 11, 2019, to March 10, 2020.

During the pandemic, the number of cases of type 2 diabetes increased by 182%, from 50 in 2019 to 141 in 2020. The average age at diagnosis was about 14 years in both time periods.

In the prepandemic period, 18 (36%) diagnosed with type 2 diabetes required inpatient admission, compared with 85 (60.3%) during the pandemic. At Children’s National, youth with suspected new-onset type 2 diabetes aren’t typically hospitalized unless they have severe hyperglycemia, ketosis, or are unable to schedule urgent outpatient follow-up, Dr. Marks noted.

The proportions of youth with new-onset type 2 diabetes who presented in diabetic ketoacidosis (DKA) rose from 2 (4%) prepandemic to 33 (23.4%) during the pandemic. Presentation with hyperosmolar DKA rose from 0 to 13 (9.2%).

However, during the pandemic only five youth were actively infected with SARS-CoV-2 at the time of type 2 diabetes diagnosis among the 90 tested.

Dr. Marks said: “We believe the increase in inpatient admissions was due to more severe presentation during the pandemic. ...We were surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
 

Shift in diagnoses to type 2 diabetes

The pandemic also appears to have shifted the proportion of youth diagnosed with type 2 diabetes, compared with type 1 diabetes. Whereas 24% of youth with new-onset diabetes prepandemic had type 2 diabetes and the rest had type 1 diabetes, during pandemic the proportion with type 2 diabetes rose to 44%.

“Rates of type 2 diabetes rose steadily at a rate of 1.45 cases per month throughout the course of the pandemic, suggesting a cumulative effect of the indirect effects of social distancing measures,” Dr. Marks said.

Furthermore, she added, whereas 60% of youth diagnosed with type 2 diabetes before the pandemic were female, the rate fell to 40% during the pandemic. This trend might be because of activity levels in that, while male adolescents are typically more active, rates of exercise fell in both sexes during the pandemic but declined more sharply in males such that activity levels between the sexes became equal.  

Although type 2 diabetes in youth has always been more common in ethnic minorities, the pandemic appears to have exacerbated these disparities.

While 58% of youth diagnosed with type 2 diabetes prepandemic identified as non-Hispanic Black, that proportion rose to 76.7% during the pandemic. Among Black youth with new-onset type 2 diabetes, 31 of 33 presented in DKA, and 12 of the 13 who presented in hyperosmolar DKA during the pandemic were Black.

“Strategies to promote health equity and address the undue burden of the COVID-19 pandemic on underserved communities must be developed to avoid worsening disparities and long-term health outcomes,” Dr. Marks said.
 

‘A microcosm’: Similar findings in a smaller population

Dr. Hsia and colleagues looked at a smaller number of patients in a shorter time period. In March–December 2019, the hospitalization rate for new-onset type 2 diabetes was 0.27% (8 out of 2,964 hospitalizations), compared with 0.62% (17 out of 2,729 hospitalizations) during the same period in 2020 (P < .048) – also more than a doubling. Age at admission, sex, and body mass index didn’t differ between the two groups.

Criteria for DKA were met by three children in 2019 versus eight in 2020, and hyperosmolar hyperglycemic syndrome in zero versus two, respectively. Mean hemoglobin A1c on admission was 12.4% in 2019 versus 13.1% in 2020 (P = .59), and mean serum glucose was 441 mg/dL versus 669 mg/dL (P = .14), respectively. Serum osmolality on admission was 314 mmol/kg in 2019 versus 335 mmol/kg in 2020 (P = .19).

“Clinically speaking the differences in the lab values were significant, but we did not have enough numbers ... to see a statistically significant difference. I think by looking at more centers, our site likely represents a microcosm of what is happening across the country,” Dr. Hsia said.

In 2019, 7 of the 8 children were African American, as were 16 of the 17 children in 2020. The other single child in each group was White.

Dr. Hsia said: “Larger studies that include more patients are needed to confirm our initial findings. More research is needed to understand why this increasing trend of type 2 diabetes diagnoses in children may be occurring [and] to better understand how stay-at-home orders and other restrictions due to COVID-19 have worsened risk factors for type 2 diabetes.”

“These include decreased physical activity, more screen time, disturbed sleep, and increased intake of processed foods, which can all lead to weight gain,” he concluded.

Dr. Marks reported receiving research support from Tandem, Dexcom, and the Cystic Fibrosis Foundation. Dr. Hsia reported no relevant financial relationships.

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

The incidence of type 2 diabetes in children appears to have doubled during the COVID-19 pandemic, data from two new U.S. studies suggest, with the lead investigator of one saying she was “surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”

Anetta_R/Thinkstock

Findings from the two separate retrospective chart reviews – one conducted in Washington, D.C., and the other in Baton Rouge, La. – were presented June 25 at the annual scientific sessions of the American Diabetes Association.

Although the two studies differed somewhat in the clinical parameters examined, both revealed a similar doubling of the rates of hospitalizations for type 2 diabetes among youth during 2020, compared with the same time period in 2019, as well as greater severity of metabolic disturbance.

And, as has been previously described with type 2 diabetes in youth, African American ethnicity predominated in both cohorts.

“Although we could not assess the cause of the increases in type 2 diabetes from our data, these disparities suggest that indirect effects of social distancing measures, including school closure and unemployment, are placing undue burden on underserved communities. Decreases in well-child care and fears of seeking medical care during the pandemic may have also contributed,” lead investigator of one of the studies, pediatric endocrinologist Brynn E. Marks, MD, Children’s National Hospital, Washington, said in an interview.
 

More hospitalizations, racial disparities aggravated by COVID-19

Lead author of the other study, Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, said in an interview: “Since the pandemic, our data suggest that more children may be diagnosed with type 2 diabetes and may require hospitalization when they are diagnosed. Looking at both datasets, there appears to be a racial disparity in type 2 diabetes diagnoses that has only been exacerbated by the COVID-19 pandemic.”

Of concern, Dr. Hsia said, “The incidence rate of type 2 diabetes in children was already on the rise before the pandemic. While there may be a brief leveling off now that children are getting regular health care and going back to school in person, I believe these rates will continue to rise especially in light of the childhood obesity rates not improving.”

Their dataset captured all youth who were newly diagnosed with type 2 diabetes during the first full year of the COVID-19 pandemic, from March 11, 2020, to March 10, 2021, and compared those data with the time period from March 11, 2019, to March 10, 2020.

During the pandemic, the number of cases of type 2 diabetes increased by 182%, from 50 in 2019 to 141 in 2020. The average age at diagnosis was about 14 years in both time periods.

In the prepandemic period, 18 (36%) diagnosed with type 2 diabetes required inpatient admission, compared with 85 (60.3%) during the pandemic. At Children’s National, youth with suspected new-onset type 2 diabetes aren’t typically hospitalized unless they have severe hyperglycemia, ketosis, or are unable to schedule urgent outpatient follow-up, Dr. Marks noted.

The proportions of youth with new-onset type 2 diabetes who presented in diabetic ketoacidosis (DKA) rose from 2 (4%) prepandemic to 33 (23.4%) during the pandemic. Presentation with hyperosmolar DKA rose from 0 to 13 (9.2%).

However, during the pandemic only five youth were actively infected with SARS-CoV-2 at the time of type 2 diabetes diagnosis among the 90 tested.

Dr. Marks said: “We believe the increase in inpatient admissions was due to more severe presentation during the pandemic. ...We were surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
 

Shift in diagnoses to type 2 diabetes

The pandemic also appears to have shifted the proportion of youth diagnosed with type 2 diabetes, compared with type 1 diabetes. Whereas 24% of youth with new-onset diabetes prepandemic had type 2 diabetes and the rest had type 1 diabetes, during pandemic the proportion with type 2 diabetes rose to 44%.

“Rates of type 2 diabetes rose steadily at a rate of 1.45 cases per month throughout the course of the pandemic, suggesting a cumulative effect of the indirect effects of social distancing measures,” Dr. Marks said.

Furthermore, she added, whereas 60% of youth diagnosed with type 2 diabetes before the pandemic were female, the rate fell to 40% during the pandemic. This trend might be because of activity levels in that, while male adolescents are typically more active, rates of exercise fell in both sexes during the pandemic but declined more sharply in males such that activity levels between the sexes became equal.  

Although type 2 diabetes in youth has always been more common in ethnic minorities, the pandemic appears to have exacerbated these disparities.

While 58% of youth diagnosed with type 2 diabetes prepandemic identified as non-Hispanic Black, that proportion rose to 76.7% during the pandemic. Among Black youth with new-onset type 2 diabetes, 31 of 33 presented in DKA, and 12 of the 13 who presented in hyperosmolar DKA during the pandemic were Black.

“Strategies to promote health equity and address the undue burden of the COVID-19 pandemic on underserved communities must be developed to avoid worsening disparities and long-term health outcomes,” Dr. Marks said.
 

‘A microcosm’: Similar findings in a smaller population

Dr. Hsia and colleagues looked at a smaller number of patients in a shorter time period. In March–December 2019, the hospitalization rate for new-onset type 2 diabetes was 0.27% (8 out of 2,964 hospitalizations), compared with 0.62% (17 out of 2,729 hospitalizations) during the same period in 2020 (P < .048) – also more than a doubling. Age at admission, sex, and body mass index didn’t differ between the two groups.

Criteria for DKA were met by three children in 2019 versus eight in 2020, and hyperosmolar hyperglycemic syndrome in zero versus two, respectively. Mean hemoglobin A1c on admission was 12.4% in 2019 versus 13.1% in 2020 (P = .59), and mean serum glucose was 441 mg/dL versus 669 mg/dL (P = .14), respectively. Serum osmolality on admission was 314 mmol/kg in 2019 versus 335 mmol/kg in 2020 (P = .19).

“Clinically speaking the differences in the lab values were significant, but we did not have enough numbers ... to see a statistically significant difference. I think by looking at more centers, our site likely represents a microcosm of what is happening across the country,” Dr. Hsia said.

In 2019, 7 of the 8 children were African American, as were 16 of the 17 children in 2020. The other single child in each group was White.

Dr. Hsia said: “Larger studies that include more patients are needed to confirm our initial findings. More research is needed to understand why this increasing trend of type 2 diabetes diagnoses in children may be occurring [and] to better understand how stay-at-home orders and other restrictions due to COVID-19 have worsened risk factors for type 2 diabetes.”

“These include decreased physical activity, more screen time, disturbed sleep, and increased intake of processed foods, which can all lead to weight gain,” he concluded.

Dr. Marks reported receiving research support from Tandem, Dexcom, and the Cystic Fibrosis Foundation. Dr. Hsia reported no relevant financial relationships.

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

Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.

“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.

“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.

SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
 

Significant differences at each dose level

Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.

One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.

The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.

The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.

The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
 

An ‘impressive’ weight loss effect

Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .

“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
 

The important issue of dose

But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.

“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.

Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.

Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.

A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
 

Low rates of hypoglycemia

Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.

These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.

Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.

SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
 

Several more tirzepatide trials

Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.

The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.

The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.

mzoler@mdedge.com

Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.

“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.

“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.

SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
 

Significant differences at each dose level

Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.

One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.

The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.

The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.

The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
 

An ‘impressive’ weight loss effect

Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .

“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
 

The important issue of dose

But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.

“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.

Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.

Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.

A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
 

Low rates of hypoglycemia

Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.

These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.

Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.

SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
 

Several more tirzepatide trials

Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.

The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.

The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.

mzoler@mdedge.com

Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.

“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.

“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.

SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
 

Significant differences at each dose level

Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.

One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.

The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.

The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.

The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
 

An ‘impressive’ weight loss effect

Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .

“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
 

The important issue of dose

But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.

“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.

Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.

Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.

A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
 

Low rates of hypoglycemia

Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.

These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.

Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.

SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
 

Several more tirzepatide trials

Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.

The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.

The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.

mzoler@mdedge.com

Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.

Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.

In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.

Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.

“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
 

Links between diabetes and COVID-19

There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.

It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.

Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m²; 87% were Hispanic.

Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
 

Impact of unmanaged diabetes and high blood glucose

Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.

Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.

COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.

The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
 

Aggressive treatment needed

Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.

“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”

Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.

“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”

Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.

Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.

Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.

In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.

Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.

“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
 

Links between diabetes and COVID-19

There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.

It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.

Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m²; 87% were Hispanic.

Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
 

Impact of unmanaged diabetes and high blood glucose

Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.

Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.

COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.

The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
 

Aggressive treatment needed

Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.

“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”

Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.

“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”

Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.

Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.

Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.

In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.

Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.

“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
 

Links between diabetes and COVID-19

There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.

It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.

Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m²; 87% were Hispanic.

Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
 

Impact of unmanaged diabetes and high blood glucose

Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.

Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.

COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.

The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
 

Aggressive treatment needed

Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.

“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”

Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.

“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”

Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.