Endocrinology

TOPLINE:

Elevated levels of plasma F2-isoprostanes, a reliable marker of oxidative stress, are associated with an increased risk for fractures in older ambulatory patients with type 2 diabetes (T2D) independently of bone density.

METHODOLOGY:

• Patients with T2D face an increased risk for fractures at any given bone mineral density; oxidative stress levels (reflected in circulating F2-isoprostanes), which are elevated in T2D, are associated with other T2D complications, and may weaken bone integrity.
• Researchers analyzed data from an observational cohort study to investigate the association between the levels of circulating F2-isoprostanes and the risk for clinical fractures in older patients with T2D.
• The data included 703 older ambulatory adults (baseline age, 70-79 years; about half White individuals and half Black individuals ; about half men and half women) from the Health, Aging and Body Composition Study, of whom 132 had T2D.
• Plasma F2-isoprostane levels were measured using baseline serum samples; bone turnover markers were also measured including procollagen type 1 N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type 1 collagen.
• Incident clinical fractures were tracked over a follow-up period of up to 17.3 years, with fractures verified through radiology reports.

TAKEAWAY:

• Overall, 25.8% patients in the T2D group and 23.5% adults in the non-diabetes group reported an incident clinical fracture during a mean follow-up period of 6.2 and 8.0 years, respectively.
• In patients with T2D, the risk for incident clinical fracture increased by 93% for every standard deviation increase in the log F2-isoprostane serum levels (hazard ratio [HR], 1.93; 95% CI, 1.26-2.95; P = .002) independently of baseline bone density, medication use, and other risk factors, with no such association reported in individuals without T2D (HR, 0.98; 95% CI, 0.81-1.18; P = .79).
• In the T2D group, elevated plasma F2-isoprostane levels were also associated with a decrease in total hip bone mineral density over 4 years (r = −0.28; P = .008), but not in the non-diabetes group.
• No correlation was found between plasma F2-isoprostane levels and circulating advanced glycoxidation end-products, bone turnover markers, or A1c levels in either group.
•  

IN PRACTICE:

“Oxidative stress in T2D may play an important role in the decline of bone quality and not just bone quantity,” the authors wrote.

SOURCE:

This study was led by Bowen Wang, PhD, Rensselaer Polytechnic Institute, Troy, New York. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

This study was conducted in a well-functioning elderly population with only White and Black participants, which may limit the generalizability of the findings to other age groups or less healthy populations. Additionally, the study did not assess prevalent vertebral fracture risk due to the small sample size. 

DISCLOSURES:

This study was supported by the US National Institute on Aging and the Intramural Research Program of the US National Institutes of Health and the Dr and Ms Sands and Sands Family for Orthopaedic Research. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated levels of plasma F2-isoprostanes, a reliable marker of oxidative stress, are associated with an increased risk for fractures in older ambulatory patients with type 2 diabetes (T2D) independently of bone density.

METHODOLOGY:

• Patients with T2D face an increased risk for fractures at any given bone mineral density; oxidative stress levels (reflected in circulating F2-isoprostanes), which are elevated in T2D, are associated with other T2D complications, and may weaken bone integrity.
• Researchers analyzed data from an observational cohort study to investigate the association between the levels of circulating F2-isoprostanes and the risk for clinical fractures in older patients with T2D.
• The data included 703 older ambulatory adults (baseline age, 70-79 years; about half White individuals and half Black individuals ; about half men and half women) from the Health, Aging and Body Composition Study, of whom 132 had T2D.
• Plasma F2-isoprostane levels were measured using baseline serum samples; bone turnover markers were also measured including procollagen type 1 N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type 1 collagen.
• Incident clinical fractures were tracked over a follow-up period of up to 17.3 years, with fractures verified through radiology reports.

TAKEAWAY:

• Overall, 25.8% patients in the T2D group and 23.5% adults in the non-diabetes group reported an incident clinical fracture during a mean follow-up period of 6.2 and 8.0 years, respectively.
• In patients with T2D, the risk for incident clinical fracture increased by 93% for every standard deviation increase in the log F2-isoprostane serum levels (hazard ratio [HR], 1.93; 95% CI, 1.26-2.95; P = .002) independently of baseline bone density, medication use, and other risk factors, with no such association reported in individuals without T2D (HR, 0.98; 95% CI, 0.81-1.18; P = .79).
• In the T2D group, elevated plasma F2-isoprostane levels were also associated with a decrease in total hip bone mineral density over 4 years (r = −0.28; P = .008), but not in the non-diabetes group.
• No correlation was found between plasma F2-isoprostane levels and circulating advanced glycoxidation end-products, bone turnover markers, or A1c levels in either group.
•  

IN PRACTICE:

“Oxidative stress in T2D may play an important role in the decline of bone quality and not just bone quantity,” the authors wrote.

SOURCE:

This study was led by Bowen Wang, PhD, Rensselaer Polytechnic Institute, Troy, New York. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

This study was conducted in a well-functioning elderly population with only White and Black participants, which may limit the generalizability of the findings to other age groups or less healthy populations. Additionally, the study did not assess prevalent vertebral fracture risk due to the small sample size. 

DISCLOSURES:

This study was supported by the US National Institute on Aging and the Intramural Research Program of the US National Institutes of Health and the Dr and Ms Sands and Sands Family for Orthopaedic Research. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated levels of plasma F2-isoprostanes, a reliable marker of oxidative stress, are associated with an increased risk for fractures in older ambulatory patients with type 2 diabetes (T2D) independently of bone density.

METHODOLOGY:

• Patients with T2D face an increased risk for fractures at any given bone mineral density; oxidative stress levels (reflected in circulating F2-isoprostanes), which are elevated in T2D, are associated with other T2D complications, and may weaken bone integrity.
• Researchers analyzed data from an observational cohort study to investigate the association between the levels of circulating F2-isoprostanes and the risk for clinical fractures in older patients with T2D.
• The data included 703 older ambulatory adults (baseline age, 70-79 years; about half White individuals and half Black individuals ; about half men and half women) from the Health, Aging and Body Composition Study, of whom 132 had T2D.
• Plasma F2-isoprostane levels were measured using baseline serum samples; bone turnover markers were also measured including procollagen type 1 N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type 1 collagen.
• Incident clinical fractures were tracked over a follow-up period of up to 17.3 years, with fractures verified through radiology reports.

TAKEAWAY:

• Overall, 25.8% patients in the T2D group and 23.5% adults in the non-diabetes group reported an incident clinical fracture during a mean follow-up period of 6.2 and 8.0 years, respectively.
• In patients with T2D, the risk for incident clinical fracture increased by 93% for every standard deviation increase in the log F2-isoprostane serum levels (hazard ratio [HR], 1.93; 95% CI, 1.26-2.95; P = .002) independently of baseline bone density, medication use, and other risk factors, with no such association reported in individuals without T2D (HR, 0.98; 95% CI, 0.81-1.18; P = .79).
• In the T2D group, elevated plasma F2-isoprostane levels were also associated with a decrease in total hip bone mineral density over 4 years (r = −0.28; P = .008), but not in the non-diabetes group.
• No correlation was found between plasma F2-isoprostane levels and circulating advanced glycoxidation end-products, bone turnover markers, or A1c levels in either group.
•  

IN PRACTICE:

“Oxidative stress in T2D may play an important role in the decline of bone quality and not just bone quantity,” the authors wrote.

SOURCE:

This study was led by Bowen Wang, PhD, Rensselaer Polytechnic Institute, Troy, New York. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

This study was conducted in a well-functioning elderly population with only White and Black participants, which may limit the generalizability of the findings to other age groups or less healthy populations. Additionally, the study did not assess prevalent vertebral fracture risk due to the small sample size. 

DISCLOSURES:

This study was supported by the US National Institute on Aging and the Intramural Research Program of the US National Institutes of Health and the Dr and Ms Sands and Sands Family for Orthopaedic Research. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.

In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”

 

Curbing Cardiovascular Drugs

The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.

But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.

Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.

“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.

 

Tapering Opioids

Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.

Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”

In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.

Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.

 

Deprescribing Benzodiazepines 

Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.

The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.

Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.

Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.

Young, Kirkwood, and Thomas reported no relevant financial relationships.

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

VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.

In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”

 

Curbing Cardiovascular Drugs

The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.

But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.

Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.

“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.

 

Tapering Opioids

Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.

Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”

In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.

Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.

 

Deprescribing Benzodiazepines 

Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.

The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.

Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.

Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.

Young, Kirkwood, and Thomas reported no relevant financial relationships.

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

VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.

In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”

 

Curbing Cardiovascular Drugs

The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.

But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.

Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.

“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.

 

Tapering Opioids

Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.

Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”

In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.

Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.

 

Deprescribing Benzodiazepines 

Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.

The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.

Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.

Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.

Young, Kirkwood, and Thomas reported no relevant financial relationships.

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

TOPLINE:

The increase in incidence of pancreatic cancer among young Americans is largely caused by improved detection of early-stage endocrine cancer, not an increase in pancreatic adenocarcinoma. Given the stable mortality rates in this population, the increase in incidence likely reflects previously undetected cases instead of a true rise in new cases, researchers say.

METHODOLOGY:

• Data from several registries have indicated that the incidence of pancreatic cancer among younger individuals, particularly women, is on the rise in the United States and worldwide.
• In a new analysis, researchers wanted to see if the observed increase in pancreatic cancer incidence among young Americans represented a true rise in cancer occurrence or indicated greater diagnostic scrutiny. If pancreatic cancer incidence is really increasing, “incidence and mortality would be expected to increase concurrently, as would early- and late-stage diagnoses,” the researchers explained.
• The researchers collected data on pancreatic cancer incidence, histology, and stage distribution for individuals aged 15-39 years from US Cancer Statistics, a database covering almost the entire US population from 2001 to 2020. Pancreatic cancer mortality data from the same timeframe came from the National Vital Statistics System.
• The researchers looked at four histologic categories: Adenocarcinoma, the dominant pancreatic cancer histology, as well as more rare subtypes — endocrine and solid pseudopapillary — and “other” category. Researchers also categorized stage-specific incidence as early stage (in situ or localized) or late stage (regional or distant).

TAKEAWAY:

• The incidence of pancreatic cancer increased 2.1-fold in young women (incidence, 3.3-6.9 per million) and 1.6-fold in young men (incidence, 3.9-6.2 per million) between 2001 and 2019. However, mortality rates remained stable for women (1.5 deaths per million; annual percent change [AAPC], −0.5%; 95% CI, –1.4% to 0.5%) and men (2.5 deaths per million; AAPC, –0.1%; 95% CI, –0.8% to 0.6%) over this period.
• Looking at cancer subtypes, the increase in incidence was largely caused by early-stage endocrine cancer and solid pseudopapillary neoplasms in women, not adenocarcinoma (which remained stable over the study period).
• Looking at cancer stage, most of the increase in incidence came from detection of smaller tumors (< 2 cm) and early-stage cancer, which rose from 0.6 to 3.7 per million in women and from 0.4 to 2.2 per million in men. The authors also found no statistically significant change in the incidence of late-stage cancer in women or men.
• Rates of surgical treatment for pancreatic cancer increased, more than tripling among women (from 1.5 to 4.7 per million) and more than doubling among men (from 1.1 to 2.3 per million).

IN PRACTICE:

“Pancreatic cancer now can be another cancer subject to overdiagnosis: The detection of disease not destined to cause symptoms or death,” the authors concluded. “Although the observed changes in incidence are small, overdiagnosis is especially concerning for pancreatic cancer, as pancreatic surgery has substantial risk for morbidity (in particular, pancreatic fistulas) and mortality.”

SOURCE:

The study, with first author Vishal R. Patel, MD, MPH, and corresponding author H. Gilbert Welch, MD, MPH, from Brigham and Women’s Hospital, Boston, was published online on November 19 in Annals of Internal Medicine.

LIMITATIONS:

The study was limited by the lack of data on the method of cancer detection, which may have affected the interpretation of the findings.

DISCLOSURES:

Disclosure forms are available with the article online.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The increase in incidence of pancreatic cancer among young Americans is largely caused by improved detection of early-stage endocrine cancer, not an increase in pancreatic adenocarcinoma. Given the stable mortality rates in this population, the increase in incidence likely reflects previously undetected cases instead of a true rise in new cases, researchers say.

METHODOLOGY:

• Data from several registries have indicated that the incidence of pancreatic cancer among younger individuals, particularly women, is on the rise in the United States and worldwide.
• In a new analysis, researchers wanted to see if the observed increase in pancreatic cancer incidence among young Americans represented a true rise in cancer occurrence or indicated greater diagnostic scrutiny. If pancreatic cancer incidence is really increasing, “incidence and mortality would be expected to increase concurrently, as would early- and late-stage diagnoses,” the researchers explained.
• The researchers collected data on pancreatic cancer incidence, histology, and stage distribution for individuals aged 15-39 years from US Cancer Statistics, a database covering almost the entire US population from 2001 to 2020. Pancreatic cancer mortality data from the same timeframe came from the National Vital Statistics System.
• The researchers looked at four histologic categories: Adenocarcinoma, the dominant pancreatic cancer histology, as well as more rare subtypes — endocrine and solid pseudopapillary — and “other” category. Researchers also categorized stage-specific incidence as early stage (in situ or localized) or late stage (regional or distant).

TAKEAWAY:

• The incidence of pancreatic cancer increased 2.1-fold in young women (incidence, 3.3-6.9 per million) and 1.6-fold in young men (incidence, 3.9-6.2 per million) between 2001 and 2019. However, mortality rates remained stable for women (1.5 deaths per million; annual percent change [AAPC], −0.5%; 95% CI, –1.4% to 0.5%) and men (2.5 deaths per million; AAPC, –0.1%; 95% CI, –0.8% to 0.6%) over this period.
• Looking at cancer subtypes, the increase in incidence was largely caused by early-stage endocrine cancer and solid pseudopapillary neoplasms in women, not adenocarcinoma (which remained stable over the study period).
• Looking at cancer stage, most of the increase in incidence came from detection of smaller tumors (< 2 cm) and early-stage cancer, which rose from 0.6 to 3.7 per million in women and from 0.4 to 2.2 per million in men. The authors also found no statistically significant change in the incidence of late-stage cancer in women or men.
• Rates of surgical treatment for pancreatic cancer increased, more than tripling among women (from 1.5 to 4.7 per million) and more than doubling among men (from 1.1 to 2.3 per million).

IN PRACTICE:

“Pancreatic cancer now can be another cancer subject to overdiagnosis: The detection of disease not destined to cause symptoms or death,” the authors concluded. “Although the observed changes in incidence are small, overdiagnosis is especially concerning for pancreatic cancer, as pancreatic surgery has substantial risk for morbidity (in particular, pancreatic fistulas) and mortality.”

SOURCE:

The study, with first author Vishal R. Patel, MD, MPH, and corresponding author H. Gilbert Welch, MD, MPH, from Brigham and Women’s Hospital, Boston, was published online on November 19 in Annals of Internal Medicine.

LIMITATIONS:

The study was limited by the lack of data on the method of cancer detection, which may have affected the interpretation of the findings.

DISCLOSURES:

Disclosure forms are available with the article online.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The increase in incidence of pancreatic cancer among young Americans is largely caused by improved detection of early-stage endocrine cancer, not an increase in pancreatic adenocarcinoma. Given the stable mortality rates in this population, the increase in incidence likely reflects previously undetected cases instead of a true rise in new cases, researchers say.

METHODOLOGY:

• Data from several registries have indicated that the incidence of pancreatic cancer among younger individuals, particularly women, is on the rise in the United States and worldwide.
• In a new analysis, researchers wanted to see if the observed increase in pancreatic cancer incidence among young Americans represented a true rise in cancer occurrence or indicated greater diagnostic scrutiny. If pancreatic cancer incidence is really increasing, “incidence and mortality would be expected to increase concurrently, as would early- and late-stage diagnoses,” the researchers explained.
• The researchers collected data on pancreatic cancer incidence, histology, and stage distribution for individuals aged 15-39 years from US Cancer Statistics, a database covering almost the entire US population from 2001 to 2020. Pancreatic cancer mortality data from the same timeframe came from the National Vital Statistics System.
• The researchers looked at four histologic categories: Adenocarcinoma, the dominant pancreatic cancer histology, as well as more rare subtypes — endocrine and solid pseudopapillary — and “other” category. Researchers also categorized stage-specific incidence as early stage (in situ or localized) or late stage (regional or distant).

TAKEAWAY:

• The incidence of pancreatic cancer increased 2.1-fold in young women (incidence, 3.3-6.9 per million) and 1.6-fold in young men (incidence, 3.9-6.2 per million) between 2001 and 2019. However, mortality rates remained stable for women (1.5 deaths per million; annual percent change [AAPC], −0.5%; 95% CI, –1.4% to 0.5%) and men (2.5 deaths per million; AAPC, –0.1%; 95% CI, –0.8% to 0.6%) over this period.
• Looking at cancer subtypes, the increase in incidence was largely caused by early-stage endocrine cancer and solid pseudopapillary neoplasms in women, not adenocarcinoma (which remained stable over the study period).
• Looking at cancer stage, most of the increase in incidence came from detection of smaller tumors (< 2 cm) and early-stage cancer, which rose from 0.6 to 3.7 per million in women and from 0.4 to 2.2 per million in men. The authors also found no statistically significant change in the incidence of late-stage cancer in women or men.
• Rates of surgical treatment for pancreatic cancer increased, more than tripling among women (from 1.5 to 4.7 per million) and more than doubling among men (from 1.1 to 2.3 per million).

IN PRACTICE:

“Pancreatic cancer now can be another cancer subject to overdiagnosis: The detection of disease not destined to cause symptoms or death,” the authors concluded. “Although the observed changes in incidence are small, overdiagnosis is especially concerning for pancreatic cancer, as pancreatic surgery has substantial risk for morbidity (in particular, pancreatic fistulas) and mortality.”

SOURCE:

The study, with first author Vishal R. Patel, MD, MPH, and corresponding author H. Gilbert Welch, MD, MPH, from Brigham and Women’s Hospital, Boston, was published online on November 19 in Annals of Internal Medicine.

LIMITATIONS:

The study was limited by the lack of data on the method of cancer detection, which may have affected the interpretation of the findings.

DISCLOSURES:

Disclosure forms are available with the article online.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Levonorgestrel intrauterine devices (IUDs) are associated with significantly more reports of acne, alopecia, and hirsutism compared with copper IUDs, with some differences between the available levonorgestrel IUDs.

METHODOLOGY:

• Researchers reviewed the US Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) through December 2023 for adverse events associated with levonorgestrel IUDs where IUDs were the only suspected cause, focusing on acne, alopecia, and hirsutism.
• They included 139,348 reports for the levonorgestrel IUDs (Mirena, Liletta, Kyleena, Skyla) and 50,450 reports for the copper IUD (Paragard).

TAKEAWAY:

• Levonorgestrel IUD users showed higher odds of reporting acne (odds ratio [OR], 3.21), alopecia (OR, 5.96), and hirsutism (OR, 15.48; all P < .0001) than copper IUD users.
• The Kyleena 19.5 mg levonorgestrel IUD was associated with the highest odds of acne reports (OR, 3.42), followed by the Mirena 52 mg (OR, 3.40) and Skyla 13.5 mg (OR, 2.30) levonorgestrel IUDs (all P < .0001).
• The Mirena IUD was associated with the highest odds of alopecia and hirsutism reports (OR, 6.62 and 17.43, respectively), followed by the Kyleena (ORs, 2.90 and 8.17, respectively) and Skyla (ORs, 2.69 and 1.48, respectively) IUDs (all P < .0001).
• Reports of acne, alopecia, and hirsutism were not significantly different between the Liletta 52 mg levonorgestrel IUD and the copper IUD.

IN PRACTICE:

“Overall, we identified significant associations between levonorgestrel IUDs and androgenic cutaneous adverse events,” the authors wrote. “Counseling prior to initiation of levonorgestrel IUDs should include information on possible cutaneous AEs including acne, alopecia, and hirsutism to guide contraceptive shared decision making,” they added.

 

SOURCE:

The study was led by Lydia Cassard, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, and was published online November 3 in Journal of the American Academy of Dermatology.

LIMITATIONS:

FAERS database reports could not be verified, and differences in FDA approval dates for IUDs could have influenced reporting rates. Moreover, a lack of data on prior medication use limits the ability to determine if these AEs are a result of changes in androgenic or antiandrogenic medication use. Cutaneous adverse events associated with copper IUDs may have been underreported because of assumptions that a nonhormonal device would not cause these adverse events.

DISCLOSURES:

The authors did not report any funding source or conflict of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Levonorgestrel intrauterine devices (IUDs) are associated with significantly more reports of acne, alopecia, and hirsutism compared with copper IUDs, with some differences between the available levonorgestrel IUDs.

METHODOLOGY:

• Researchers reviewed the US Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) through December 2023 for adverse events associated with levonorgestrel IUDs where IUDs were the only suspected cause, focusing on acne, alopecia, and hirsutism.
• They included 139,348 reports for the levonorgestrel IUDs (Mirena, Liletta, Kyleena, Skyla) and 50,450 reports for the copper IUD (Paragard).

TAKEAWAY:

• Levonorgestrel IUD users showed higher odds of reporting acne (odds ratio [OR], 3.21), alopecia (OR, 5.96), and hirsutism (OR, 15.48; all P < .0001) than copper IUD users.
• The Kyleena 19.5 mg levonorgestrel IUD was associated with the highest odds of acne reports (OR, 3.42), followed by the Mirena 52 mg (OR, 3.40) and Skyla 13.5 mg (OR, 2.30) levonorgestrel IUDs (all P < .0001).
• The Mirena IUD was associated with the highest odds of alopecia and hirsutism reports (OR, 6.62 and 17.43, respectively), followed by the Kyleena (ORs, 2.90 and 8.17, respectively) and Skyla (ORs, 2.69 and 1.48, respectively) IUDs (all P < .0001).
• Reports of acne, alopecia, and hirsutism were not significantly different between the Liletta 52 mg levonorgestrel IUD and the copper IUD.

IN PRACTICE:

“Overall, we identified significant associations between levonorgestrel IUDs and androgenic cutaneous adverse events,” the authors wrote. “Counseling prior to initiation of levonorgestrel IUDs should include information on possible cutaneous AEs including acne, alopecia, and hirsutism to guide contraceptive shared decision making,” they added.

 

SOURCE:

The study was led by Lydia Cassard, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, and was published online November 3 in Journal of the American Academy of Dermatology.

LIMITATIONS:

FAERS database reports could not be verified, and differences in FDA approval dates for IUDs could have influenced reporting rates. Moreover, a lack of data on prior medication use limits the ability to determine if these AEs are a result of changes in androgenic or antiandrogenic medication use. Cutaneous adverse events associated with copper IUDs may have been underreported because of assumptions that a nonhormonal device would not cause these adverse events.

DISCLOSURES:

The authors did not report any funding source or conflict of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Levonorgestrel intrauterine devices (IUDs) are associated with significantly more reports of acne, alopecia, and hirsutism compared with copper IUDs, with some differences between the available levonorgestrel IUDs.

METHODOLOGY:

• Researchers reviewed the US Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) through December 2023 for adverse events associated with levonorgestrel IUDs where IUDs were the only suspected cause, focusing on acne, alopecia, and hirsutism.
• They included 139,348 reports for the levonorgestrel IUDs (Mirena, Liletta, Kyleena, Skyla) and 50,450 reports for the copper IUD (Paragard).

TAKEAWAY:

• Levonorgestrel IUD users showed higher odds of reporting acne (odds ratio [OR], 3.21), alopecia (OR, 5.96), and hirsutism (OR, 15.48; all P < .0001) than copper IUD users.
• The Kyleena 19.5 mg levonorgestrel IUD was associated with the highest odds of acne reports (OR, 3.42), followed by the Mirena 52 mg (OR, 3.40) and Skyla 13.5 mg (OR, 2.30) levonorgestrel IUDs (all P < .0001).
• The Mirena IUD was associated with the highest odds of alopecia and hirsutism reports (OR, 6.62 and 17.43, respectively), followed by the Kyleena (ORs, 2.90 and 8.17, respectively) and Skyla (ORs, 2.69 and 1.48, respectively) IUDs (all P < .0001).
• Reports of acne, alopecia, and hirsutism were not significantly different between the Liletta 52 mg levonorgestrel IUD and the copper IUD.

IN PRACTICE:

“Overall, we identified significant associations between levonorgestrel IUDs and androgenic cutaneous adverse events,” the authors wrote. “Counseling prior to initiation of levonorgestrel IUDs should include information on possible cutaneous AEs including acne, alopecia, and hirsutism to guide contraceptive shared decision making,” they added.

 

SOURCE:

The study was led by Lydia Cassard, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, and was published online November 3 in Journal of the American Academy of Dermatology.

LIMITATIONS:

FAERS database reports could not be verified, and differences in FDA approval dates for IUDs could have influenced reporting rates. Moreover, a lack of data on prior medication use limits the ability to determine if these AEs are a result of changes in androgenic or antiandrogenic medication use. Cutaneous adverse events associated with copper IUDs may have been underreported because of assumptions that a nonhormonal device would not cause these adverse events.

DISCLOSURES:

The authors did not report any funding source or conflict of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The use of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), is not associated with an increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) in patients with type 2 diabetes, obesity, or both conditions.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the TriNetX Analytics Network to investigate the potential risk for NAION associated with semaglutide use in a broader population worldwide.
• They included Caucasians aged ≥ 18 years with only type 2 diabetes (n = 37,245) , only obesity (n = 138,391), or both (n = 64,989) who visited healthcare facilities three or more times.
• The participants were further grouped into those prescribed semaglutide and those using non–GLP-1 RA medications.
• Propensity score matching was performed to balance age, sex, body mass index, A1C levels, medications, and underlying comorbidities between the participants using semaglutide or non–GLP-1 RAs.
• The main outcome measure was the occurrence of NAION, evaluated at 1, 2, and 3 years of follow-up.

TAKEAWAY:

• The use of semaglutide vs non–GLP-1 RAs was not associated with an increased risk for NAION in people with only type 2 diabetes during the 1-year (hazard ratio [HR], 2.32; 95% CI, 0.60-8.97), 2-year (HR, 2.31; 95% CI, 0.86-6.17), and 3-year (HR, 1.51; 0.71-3.25) follow-up periods.
• Similarly, in the obesity-only cohort, use of semaglutide was not linked to the development of NAION across 1-year (HR, 0.41; 95% CI, 0.08-2.09), 2-year (HR, 0.67; 95% CI, 0.20-2.24), and 3-year (HR, 0.72; 95% CI, 0.24-2.17) follow-up periods.
• The patients with both diabetes and obesity also showed no significant association between use of semaglutide and the risk for NAION across each follow-up period.
• Sensitivity analysis confirmed the prescription of semaglutide was not associated with an increased risk for NAION compared with non–GLP-1 RA medications.

IN PRACTICE:

“Our large, multinational, population-based, real-world study found that semaglutide is not associated with an increased risk of NAION in the general population,” the authors of the study wrote.

SOURCE:

The study was led by Chien-Chih Chou, MD, PhD, of National Yang Ming Chiao Tung University, in Taipei City, Taiwan, and was published online on November 02, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study may have limited the ability to establish causality between the use of semaglutide and the risk for NAION. The reliance on diagnosis coding for NAION may have introduced a potential misclassification of cases. Moreover, approximately half of the healthcare organizations in the TriNetX network are based in the United States, potentially limiting the diversity of the data.

DISCLOSURES:

This study was supported by a grant from Taichung Veterans General Hospital. The authors declared no potential conflicts of interest.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The use of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), is not associated with an increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) in patients with type 2 diabetes, obesity, or both conditions.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the TriNetX Analytics Network to investigate the potential risk for NAION associated with semaglutide use in a broader population worldwide.
• They included Caucasians aged ≥ 18 years with only type 2 diabetes (n = 37,245) , only obesity (n = 138,391), or both (n = 64,989) who visited healthcare facilities three or more times.
• The participants were further grouped into those prescribed semaglutide and those using non–GLP-1 RA medications.
• Propensity score matching was performed to balance age, sex, body mass index, A1C levels, medications, and underlying comorbidities between the participants using semaglutide or non–GLP-1 RAs.
• The main outcome measure was the occurrence of NAION, evaluated at 1, 2, and 3 years of follow-up.

TAKEAWAY:

• The use of semaglutide vs non–GLP-1 RAs was not associated with an increased risk for NAION in people with only type 2 diabetes during the 1-year (hazard ratio [HR], 2.32; 95% CI, 0.60-8.97), 2-year (HR, 2.31; 95% CI, 0.86-6.17), and 3-year (HR, 1.51; 0.71-3.25) follow-up periods.
• Similarly, in the obesity-only cohort, use of semaglutide was not linked to the development of NAION across 1-year (HR, 0.41; 95% CI, 0.08-2.09), 2-year (HR, 0.67; 95% CI, 0.20-2.24), and 3-year (HR, 0.72; 95% CI, 0.24-2.17) follow-up periods.
• The patients with both diabetes and obesity also showed no significant association between use of semaglutide and the risk for NAION across each follow-up period.
• Sensitivity analysis confirmed the prescription of semaglutide was not associated with an increased risk for NAION compared with non–GLP-1 RA medications.

IN PRACTICE:

“Our large, multinational, population-based, real-world study found that semaglutide is not associated with an increased risk of NAION in the general population,” the authors of the study wrote.

SOURCE:

The study was led by Chien-Chih Chou, MD, PhD, of National Yang Ming Chiao Tung University, in Taipei City, Taiwan, and was published online on November 02, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study may have limited the ability to establish causality between the use of semaglutide and the risk for NAION. The reliance on diagnosis coding for NAION may have introduced a potential misclassification of cases. Moreover, approximately half of the healthcare organizations in the TriNetX network are based in the United States, potentially limiting the diversity of the data.

DISCLOSURES:

This study was supported by a grant from Taichung Veterans General Hospital. The authors declared no potential conflicts of interest.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The use of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), is not associated with an increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) in patients with type 2 diabetes, obesity, or both conditions.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the TriNetX Analytics Network to investigate the potential risk for NAION associated with semaglutide use in a broader population worldwide.
• They included Caucasians aged ≥ 18 years with only type 2 diabetes (n = 37,245) , only obesity (n = 138,391), or both (n = 64,989) who visited healthcare facilities three or more times.
• The participants were further grouped into those prescribed semaglutide and those using non–GLP-1 RA medications.
• Propensity score matching was performed to balance age, sex, body mass index, A1C levels, medications, and underlying comorbidities between the participants using semaglutide or non–GLP-1 RAs.
• The main outcome measure was the occurrence of NAION, evaluated at 1, 2, and 3 years of follow-up.

TAKEAWAY:

• The use of semaglutide vs non–GLP-1 RAs was not associated with an increased risk for NAION in people with only type 2 diabetes during the 1-year (hazard ratio [HR], 2.32; 95% CI, 0.60-8.97), 2-year (HR, 2.31; 95% CI, 0.86-6.17), and 3-year (HR, 1.51; 0.71-3.25) follow-up periods.
• Similarly, in the obesity-only cohort, use of semaglutide was not linked to the development of NAION across 1-year (HR, 0.41; 95% CI, 0.08-2.09), 2-year (HR, 0.67; 95% CI, 0.20-2.24), and 3-year (HR, 0.72; 95% CI, 0.24-2.17) follow-up periods.
• The patients with both diabetes and obesity also showed no significant association between use of semaglutide and the risk for NAION across each follow-up period.
• Sensitivity analysis confirmed the prescription of semaglutide was not associated with an increased risk for NAION compared with non–GLP-1 RA medications.

IN PRACTICE:

“Our large, multinational, population-based, real-world study found that semaglutide is not associated with an increased risk of NAION in the general population,” the authors of the study wrote.

SOURCE:

The study was led by Chien-Chih Chou, MD, PhD, of National Yang Ming Chiao Tung University, in Taipei City, Taiwan, and was published online on November 02, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study may have limited the ability to establish causality between the use of semaglutide and the risk for NAION. The reliance on diagnosis coding for NAION may have introduced a potential misclassification of cases. Moreover, approximately half of the healthcare organizations in the TriNetX network are based in the United States, potentially limiting the diversity of the data.

DISCLOSURES:

This study was supported by a grant from Taichung Veterans General Hospital. The authors declared no potential conflicts of interest.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Consumption of ultraprocessed foods (UPFs), such as carbonated drinks, processed meats, and sweet or savory packaged snacks, is associated with accelerated biological aging, as measured by 36 blood-based biomarkers, and factors other than poor nutritional content may be to blame.

METHODOLOGY:

• Previous studies have reported an association between high consumption of UPFs and some measures of early biological aging, such as shorter telomere length, cognitive decline, and frailty, but the relationship is largely unexplored so far, including exactly how UPFs may harm health.
• To examine the association between UPF consumption and biological aging, researchers conducted a cross-sectional analysis of 22,495 participants (mean chronological age, 55.6 years; 52% women) from the Moli-sani Study in Italy, who were recruited between 2005 and 2010.
• Food intake was assessed with a food frequency questionnaire that covered 188 different food items, each of which was categorized into one of four groups based on the extent of processing, ranging from minimally processed foods, such as fruits, vegetables, meat and fish, to UPFs.
• UPF intake was determined by weight, using the ratio of UPFs to the total weight of food and beverages (g/d), and participants were categorized into sex-specific fifths according to the proportion of UPFs in their total food intake. Diet quality was also evaluated using the Mediterranean Diet Score.
• Biological age was computed using a deep neural network approach based on 36 circulating blood biomarkers, and the mean difference between the mean biological and chronological ages was analyzed.

TAKEAWAY:

• The mean difference between biological and chronological ages of the participants was –0.70 years.
• Higher intake of UPFs was associated with accelerated biological aging compared with the lowest intake (regression coefficient, 0.34; 95% CI, 0.08-0.61), with a mean difference between the biological and chronological ages of −4.1 years and 1.6 years in those with the lowest and highest intakes, respectively.
• The association between UPF consumption and biological aging was nonlinear (P = .049 for nonlinearity). The association tended to be stronger in men than in women, but this was not statistically significant.
• Including the Mediterranean Diet Score in the model slightly attenuated the association by 9.1%, indicating that poor nutritional content was likely to explain a small part of the underlying mechanism.

IN PRACTICE:

“Our results showed that the UPFs–biological aging association was weakly explained by the poor nutritional composition of these highly processed foods, suggesting that biological aging could be mainly influenced by non-nutrient food characteristics, which include altered food matrix, contact materials and neo-formed compounds,” the authors wrote.

 

SOURCE:

The study was led by Simona Esposito, Research Unit of Epidemiology and Prevention, IRCCS Neuromed, Isernia, Italy. It was published online in The American Journal of Clinical Nutrition.

 

LIMITATIONS:

The cross-sectional design of the study limited the ability to determine the temporal directionality of the association, and the observational nature of the study limited the ability to establish the causality between UPF consumption and biological aging. The use of self-reported dietary data may have introduced recall bias. The study population was limited to adults from Central-Southern Italy, which may affect the generalizability of the findings.

 

DISCLOSURES:

The study was developed within the project funded by the Next Generation European Union “Age-It — Ageing well in an ageing society” project, National Recovery and Resilience Plan. The analyses were partially supported by the Italian Ministry of Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Consumption of ultraprocessed foods (UPFs), such as carbonated drinks, processed meats, and sweet or savory packaged snacks, is associated with accelerated biological aging, as measured by 36 blood-based biomarkers, and factors other than poor nutritional content may be to blame.

METHODOLOGY:

• Previous studies have reported an association between high consumption of UPFs and some measures of early biological aging, such as shorter telomere length, cognitive decline, and frailty, but the relationship is largely unexplored so far, including exactly how UPFs may harm health.
• To examine the association between UPF consumption and biological aging, researchers conducted a cross-sectional analysis of 22,495 participants (mean chronological age, 55.6 years; 52% women) from the Moli-sani Study in Italy, who were recruited between 2005 and 2010.
• Food intake was assessed with a food frequency questionnaire that covered 188 different food items, each of which was categorized into one of four groups based on the extent of processing, ranging from minimally processed foods, such as fruits, vegetables, meat and fish, to UPFs.
• UPF intake was determined by weight, using the ratio of UPFs to the total weight of food and beverages (g/d), and participants were categorized into sex-specific fifths according to the proportion of UPFs in their total food intake. Diet quality was also evaluated using the Mediterranean Diet Score.
• Biological age was computed using a deep neural network approach based on 36 circulating blood biomarkers, and the mean difference between the mean biological and chronological ages was analyzed.

TAKEAWAY:

• The mean difference between biological and chronological ages of the participants was –0.70 years.
• Higher intake of UPFs was associated with accelerated biological aging compared with the lowest intake (regression coefficient, 0.34; 95% CI, 0.08-0.61), with a mean difference between the biological and chronological ages of −4.1 years and 1.6 years in those with the lowest and highest intakes, respectively.
• The association between UPF consumption and biological aging was nonlinear (P = .049 for nonlinearity). The association tended to be stronger in men than in women, but this was not statistically significant.
• Including the Mediterranean Diet Score in the model slightly attenuated the association by 9.1%, indicating that poor nutritional content was likely to explain a small part of the underlying mechanism.

IN PRACTICE:

“Our results showed that the UPFs–biological aging association was weakly explained by the poor nutritional composition of these highly processed foods, suggesting that biological aging could be mainly influenced by non-nutrient food characteristics, which include altered food matrix, contact materials and neo-formed compounds,” the authors wrote.

 

SOURCE:

The study was led by Simona Esposito, Research Unit of Epidemiology and Prevention, IRCCS Neuromed, Isernia, Italy. It was published online in The American Journal of Clinical Nutrition.

 

LIMITATIONS:

The cross-sectional design of the study limited the ability to determine the temporal directionality of the association, and the observational nature of the study limited the ability to establish the causality between UPF consumption and biological aging. The use of self-reported dietary data may have introduced recall bias. The study population was limited to adults from Central-Southern Italy, which may affect the generalizability of the findings.

 

DISCLOSURES:

The study was developed within the project funded by the Next Generation European Union “Age-It — Ageing well in an ageing society” project, National Recovery and Resilience Plan. The analyses were partially supported by the Italian Ministry of Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Consumption of ultraprocessed foods (UPFs), such as carbonated drinks, processed meats, and sweet or savory packaged snacks, is associated with accelerated biological aging, as measured by 36 blood-based biomarkers, and factors other than poor nutritional content may be to blame.

METHODOLOGY:

• Previous studies have reported an association between high consumption of UPFs and some measures of early biological aging, such as shorter telomere length, cognitive decline, and frailty, but the relationship is largely unexplored so far, including exactly how UPFs may harm health.
• To examine the association between UPF consumption and biological aging, researchers conducted a cross-sectional analysis of 22,495 participants (mean chronological age, 55.6 years; 52% women) from the Moli-sani Study in Italy, who were recruited between 2005 and 2010.
• Food intake was assessed with a food frequency questionnaire that covered 188 different food items, each of which was categorized into one of four groups based on the extent of processing, ranging from minimally processed foods, such as fruits, vegetables, meat and fish, to UPFs.
• UPF intake was determined by weight, using the ratio of UPFs to the total weight of food and beverages (g/d), and participants were categorized into sex-specific fifths according to the proportion of UPFs in their total food intake. Diet quality was also evaluated using the Mediterranean Diet Score.
• Biological age was computed using a deep neural network approach based on 36 circulating blood biomarkers, and the mean difference between the mean biological and chronological ages was analyzed.

TAKEAWAY:

• The mean difference between biological and chronological ages of the participants was –0.70 years.
• Higher intake of UPFs was associated with accelerated biological aging compared with the lowest intake (regression coefficient, 0.34; 95% CI, 0.08-0.61), with a mean difference between the biological and chronological ages of −4.1 years and 1.6 years in those with the lowest and highest intakes, respectively.
• The association between UPF consumption and biological aging was nonlinear (P = .049 for nonlinearity). The association tended to be stronger in men than in women, but this was not statistically significant.
• Including the Mediterranean Diet Score in the model slightly attenuated the association by 9.1%, indicating that poor nutritional content was likely to explain a small part of the underlying mechanism.

IN PRACTICE:

“Our results showed that the UPFs–biological aging association was weakly explained by the poor nutritional composition of these highly processed foods, suggesting that biological aging could be mainly influenced by non-nutrient food characteristics, which include altered food matrix, contact materials and neo-formed compounds,” the authors wrote.

 

SOURCE:

The study was led by Simona Esposito, Research Unit of Epidemiology and Prevention, IRCCS Neuromed, Isernia, Italy. It was published online in The American Journal of Clinical Nutrition.

 

LIMITATIONS:

The cross-sectional design of the study limited the ability to determine the temporal directionality of the association, and the observational nature of the study limited the ability to establish the causality between UPF consumption and biological aging. The use of self-reported dietary data may have introduced recall bias. The study population was limited to adults from Central-Southern Italy, which may affect the generalizability of the findings.

 

DISCLOSURES:

The study was developed within the project funded by the Next Generation European Union “Age-It — Ageing well in an ageing society” project, National Recovery and Resilience Plan. The analyses were partially supported by the Italian Ministry of Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

Patients who discontinue treatment with the osteoporosis drug denosumab, despite transitioning to zoledronate, show significant losses in lumbar spine bone mineral density (BMD) within a year, according to the latest findings to show that the rapid rebound of bone loss after denosumab discontinuation is not easily prevented with other therapies — even bisphosphonates.

“When initiating denosumab for osteoporosis treatment, it is recommended to engage in thorough shared decision-making with the patient to ensure they understand the potential risks associated with discontinuing the medication,” senior author Shau-Huai Fu, MD, PhD, Department of Orthopedics, National Taiwan University Hospital Yunlin Branch, Douliu, told this news organization.

Furthermore, “integrating a case manager system is crucial to support long-term adherence and compliance,” he added.

The results are from the Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial, published online in JAMA Network Open.

In the study, 101 patients were recruited between April 2019 and May 2021 at a referral center and two hospitals in Taiwan. The patients, including postmenopausal women and men over the age of 50, had been treated with regular denosumab for at least 2 years and had no previous exposure to other anti-osteoporosis medication.

They were randomized to treatment either with continuous denosumab at the standard dose of 60 mg twice yearly or to discontinue denosumab and receive the standard intravenous dose of the bisphosphonate zoledronate at 5 mg at the time when the next dose of denosumab would have been administered.

There were no differences between the two groups in serum bone turnover markers at baseline.

The current results, reflecting the first year of the 2-year study, show that, overall, those receiving zoledronate (n = 76), had a significant decrease in lumbar spine BMD, compared with a slight increase in the denosumab continuation group (–0.68% vs 1.30%, respectively; P = .03).

No significant differences were observed between the groups in terms of the study’s other measures of total hip BMD (median, 0% vs 1.12%; P = .24), and femoral neck BMD (median, 0.18% vs 0.17%; P = .71).

Additional findings from multivariable analyses in the study also supported results from previous studies showing that a longer duration of denosumab use is associated with a more substantial rebound effect: Among 15 of the denosumab users in the study who had ≥ 3 prior years of the drug, the reduction in lumbar spine BMD was even greater with zoledronate compared with denosumab continuation (–3.20% vs 1.30%; P = .003).

Though the lack of losses in the other measures of total hip and femoral neck BMD may seem encouraging, evidence from the bulk of other studies suggests cautious interpretation of those findings, Fu said.

“Although our study did not observe a noticeable decline in total hip or femoral neck BMD, other randomized controlled trials with longer durations of denosumab use have reported significant reductions in these areas,” Fu said. “Therefore, it cannot be assumed that non-lumbar spine regions are entirely safe.”

 

Fracture Risk Is the Overriding Concern

Meanwhile, the loss of lumbar spine BMD is of particular concern because of its role in what amounts to the broader, overriding concern of denosumab discontinuation — the risk for fracture, Fu noted.

“Real-world observations indicate that fractures caused by or associated with discontinuation of denosumab primarily occur in the spine,” he explained.

Previous research underscores the risk for fracture with denosumab discontinuation — and the greater risk with longer-term denosumab use, showing an 11.8% annual incidence of vertebral fracture after discontinuation of denosumab used for less than 2 years, increasing to 16.0% upon discontinuation after more than 2 years of treatment.

Randomized trials have shown sequential zoledronate to have some benefit in offsetting that risk, reducing first-year fracture risk by 3%-4% in some studies.

In the current study, 3 of 76 participants experienced a vertebral fracture in the first year of discontinuation, all involving women, including 2 who had been receiving denosumab for ≥ 4 years before medication transition.

If a transition to a bisphosphonate is anticipated, the collective findings suggest doing it as early on in denosumab treatment as possible, Fu and his colleagues noted in the study.

“When medication transition from denosumab is expected or when long-term denosumab treatment may not be suitable, earlier medication transition with potent sequential therapy should be considered,” they wrote.

 

Dosing Adjustments?

The findings add to the evidence that “patients who gain the most with denosumab are likely to lose the most with zoledronate,” Nelson Watts, MD, who authored an editorial accompanying the study, told this news organization.

Furthermore, “denosumab and other medications seem to do more [and faster] for BMD in the spine, so we expect more loss in the spine than in the hip,” said Watts, who is director of Mercy Health Osteoporosis and Bone Health Services, Bon Secours Mercy Health in Cincinnati, Ohio.

“Studies are needed but not yet done to see if a higher dose or more frequent zoledronate would be better for BMD than the ‘usual’ yearly dose,” Watts added.

The only published clinical recommendations on the matter are discussed in a position paper from the European Calcified Tissue Society (ECTS).

“Pending additional robust data, a pragmatic approach is to begin treatment with zoledronate 6 months after the last denosumab injection and monitor the effect with bone turnover markers, for example, 3 and 6 months after the zoledronate infusion,” they recommended.

In cases of increased bone turnover markers, including above the mean found in age- and sex-matched cohorts, “repeated infusion of zoledronate should be considered,” the society added.

If bone turnover markers are not available for monitoring the patients, “a pragmatic approach could be administrating a second infusion of zoledronate 6 months after the first infusion,” they wrote.

 

Clinicians Need to Be Proactive From the Start

Bente Langdahl, MD, of the Medical Department of Endocrinology, Aarhus University Hospital in Denmark, who was a coauthor on the ECTS position statement, told this news organization that clinicians should also be proactive on the other side of treatment — before it begins — to prevent problems with discontinuation.

“I think denosumab is a very good treatment for some patients with high fracture risk and very low BMD, but both patients and clinicians should know that this treatment is either lifelong or there needs to be a plan for discontinuation,” Langdahl said.

Langdahl noted that denosumab is coming off patent soon; hence, issues with cost could become more manageable.

But until then, “I think [cost] should be considered before starting treatment because if patients cannot afford denosumab, they should have been started on zoledronate from the beginning.”

 

Discontinuation Reasons Vary

Research indicates that, broadly, adherence to denosumab ranges from about 45% to 72% at 2 years, with some reasons for discontinuation including the need for dental treatment or cost, Fu and colleagues reported.

Fu added, however, that other reasons for discontinuing denosumab “are not due to ‘need’ but rather factors such as relocating, missing follow-up appointments, or poor adherence.”

Lorenz Hofbauer, MD, who is head of the Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III at the Technical University Medical Center in Dresden, Germany, noted that another issue contributing to some hesitation by patients about remaining on, or even initiating denosumab, is the known risk for osteonecrosis of the jaw (ONJ).

Though reported as being rare, research continuing to stir concern for ONJ with denosumab use includes one recent study of patients with breast cancer showing those treated with denosumab had a fivefold higher risk for ONJ vs those on bisphosphonates.

“About 20% of my patients have ONJ concerns or other questions, which may delay treatment with denosumab or other therapies,” Hofbauer told this news organization.

“There is a high need to discuss risk versus benefits toward a shared decision-making,” he said.

Conversely, however, Hofbauer noted that adherence to denosumab at his center is fairly high — at 90%, which he says is largely credited to an electronically supported recall system in place at the center.

Denosumab maker Amgen also offers patient reminders via email, text, or phone through its Bone Matters patient support system, which also provides access to a call center for questions or to update treatment appointment information.

In terms of the ongoing question of how to best prevent fracture risk when patients do wind up discontinuing denosumab, Watts concluded in his editorial that more robust studies are needed.

“The dilemma is what to do with longer-term users who stop, and the real question is not what happens to BMD, but what happens to fracture risk,” he wrote.

“It is unlikely that the fracture risk question can be answered due to ethical limitations, but finding the best option, [whether it is] oral or intravenous bisphosphonate, timing, dose, and frequency, to minimize bone loss and the rebound increase in bone resorption after stopping long-term denosumab requires larger and longer studies of better design.”

The authors had no disclosures to report. Watts has been an investigator, consultant, and speaker for Amgen outside of the published editorial. Hofbauer is on advisory boards for Alexion Pharmaceuticals, Amolyt Pharma, Amgen, and UCB. Langdahl has been a primary investigator on previous and ongoing clinical trials involving denosumab.

A version of this article appeared on Medscape.com.

Patients who discontinue treatment with the osteoporosis drug denosumab, despite transitioning to zoledronate, show significant losses in lumbar spine bone mineral density (BMD) within a year, according to the latest findings to show that the rapid rebound of bone loss after denosumab discontinuation is not easily prevented with other therapies — even bisphosphonates.

“When initiating denosumab for osteoporosis treatment, it is recommended to engage in thorough shared decision-making with the patient to ensure they understand the potential risks associated with discontinuing the medication,” senior author Shau-Huai Fu, MD, PhD, Department of Orthopedics, National Taiwan University Hospital Yunlin Branch, Douliu, told this news organization.

Furthermore, “integrating a case manager system is crucial to support long-term adherence and compliance,” he added.

The results are from the Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial, published online in JAMA Network Open.

In the study, 101 patients were recruited between April 2019 and May 2021 at a referral center and two hospitals in Taiwan. The patients, including postmenopausal women and men over the age of 50, had been treated with regular denosumab for at least 2 years and had no previous exposure to other anti-osteoporosis medication.

They were randomized to treatment either with continuous denosumab at the standard dose of 60 mg twice yearly or to discontinue denosumab and receive the standard intravenous dose of the bisphosphonate zoledronate at 5 mg at the time when the next dose of denosumab would have been administered.

There were no differences between the two groups in serum bone turnover markers at baseline.

The current results, reflecting the first year of the 2-year study, show that, overall, those receiving zoledronate (n = 76), had a significant decrease in lumbar spine BMD, compared with a slight increase in the denosumab continuation group (–0.68% vs 1.30%, respectively; P = .03).

No significant differences were observed between the groups in terms of the study’s other measures of total hip BMD (median, 0% vs 1.12%; P = .24), and femoral neck BMD (median, 0.18% vs 0.17%; P = .71).

Additional findings from multivariable analyses in the study also supported results from previous studies showing that a longer duration of denosumab use is associated with a more substantial rebound effect: Among 15 of the denosumab users in the study who had ≥ 3 prior years of the drug, the reduction in lumbar spine BMD was even greater with zoledronate compared with denosumab continuation (–3.20% vs 1.30%; P = .003).

Though the lack of losses in the other measures of total hip and femoral neck BMD may seem encouraging, evidence from the bulk of other studies suggests cautious interpretation of those findings, Fu said.

“Although our study did not observe a noticeable decline in total hip or femoral neck BMD, other randomized controlled trials with longer durations of denosumab use have reported significant reductions in these areas,” Fu said. “Therefore, it cannot be assumed that non-lumbar spine regions are entirely safe.”

 

Fracture Risk Is the Overriding Concern

Meanwhile, the loss of lumbar spine BMD is of particular concern because of its role in what amounts to the broader, overriding concern of denosumab discontinuation — the risk for fracture, Fu noted.

“Real-world observations indicate that fractures caused by or associated with discontinuation of denosumab primarily occur in the spine,” he explained.

Previous research underscores the risk for fracture with denosumab discontinuation — and the greater risk with longer-term denosumab use, showing an 11.8% annual incidence of vertebral fracture after discontinuation of denosumab used for less than 2 years, increasing to 16.0% upon discontinuation after more than 2 years of treatment.

Randomized trials have shown sequential zoledronate to have some benefit in offsetting that risk, reducing first-year fracture risk by 3%-4% in some studies.

In the current study, 3 of 76 participants experienced a vertebral fracture in the first year of discontinuation, all involving women, including 2 who had been receiving denosumab for ≥ 4 years before medication transition.

If a transition to a bisphosphonate is anticipated, the collective findings suggest doing it as early on in denosumab treatment as possible, Fu and his colleagues noted in the study.

“When medication transition from denosumab is expected or when long-term denosumab treatment may not be suitable, earlier medication transition with potent sequential therapy should be considered,” they wrote.

 

Dosing Adjustments?

The findings add to the evidence that “patients who gain the most with denosumab are likely to lose the most with zoledronate,” Nelson Watts, MD, who authored an editorial accompanying the study, told this news organization.

Furthermore, “denosumab and other medications seem to do more [and faster] for BMD in the spine, so we expect more loss in the spine than in the hip,” said Watts, who is director of Mercy Health Osteoporosis and Bone Health Services, Bon Secours Mercy Health in Cincinnati, Ohio.

“Studies are needed but not yet done to see if a higher dose or more frequent zoledronate would be better for BMD than the ‘usual’ yearly dose,” Watts added.

The only published clinical recommendations on the matter are discussed in a position paper from the European Calcified Tissue Society (ECTS).

“Pending additional robust data, a pragmatic approach is to begin treatment with zoledronate 6 months after the last denosumab injection and monitor the effect with bone turnover markers, for example, 3 and 6 months after the zoledronate infusion,” they recommended.

In cases of increased bone turnover markers, including above the mean found in age- and sex-matched cohorts, “repeated infusion of zoledronate should be considered,” the society added.

If bone turnover markers are not available for monitoring the patients, “a pragmatic approach could be administrating a second infusion of zoledronate 6 months after the first infusion,” they wrote.

 

Clinicians Need to Be Proactive From the Start

Bente Langdahl, MD, of the Medical Department of Endocrinology, Aarhus University Hospital in Denmark, who was a coauthor on the ECTS position statement, told this news organization that clinicians should also be proactive on the other side of treatment — before it begins — to prevent problems with discontinuation.

“I think denosumab is a very good treatment for some patients with high fracture risk and very low BMD, but both patients and clinicians should know that this treatment is either lifelong or there needs to be a plan for discontinuation,” Langdahl said.

Langdahl noted that denosumab is coming off patent soon; hence, issues with cost could become more manageable.

But until then, “I think [cost] should be considered before starting treatment because if patients cannot afford denosumab, they should have been started on zoledronate from the beginning.”

 

Discontinuation Reasons Vary

Research indicates that, broadly, adherence to denosumab ranges from about 45% to 72% at 2 years, with some reasons for discontinuation including the need for dental treatment or cost, Fu and colleagues reported.

Fu added, however, that other reasons for discontinuing denosumab “are not due to ‘need’ but rather factors such as relocating, missing follow-up appointments, or poor adherence.”

Lorenz Hofbauer, MD, who is head of the Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III at the Technical University Medical Center in Dresden, Germany, noted that another issue contributing to some hesitation by patients about remaining on, or even initiating denosumab, is the known risk for osteonecrosis of the jaw (ONJ).

Though reported as being rare, research continuing to stir concern for ONJ with denosumab use includes one recent study of patients with breast cancer showing those treated with denosumab had a fivefold higher risk for ONJ vs those on bisphosphonates.

“About 20% of my patients have ONJ concerns or other questions, which may delay treatment with denosumab or other therapies,” Hofbauer told this news organization.

“There is a high need to discuss risk versus benefits toward a shared decision-making,” he said.

Conversely, however, Hofbauer noted that adherence to denosumab at his center is fairly high — at 90%, which he says is largely credited to an electronically supported recall system in place at the center.

Denosumab maker Amgen also offers patient reminders via email, text, or phone through its Bone Matters patient support system, which also provides access to a call center for questions or to update treatment appointment information.

In terms of the ongoing question of how to best prevent fracture risk when patients do wind up discontinuing denosumab, Watts concluded in his editorial that more robust studies are needed.

“The dilemma is what to do with longer-term users who stop, and the real question is not what happens to BMD, but what happens to fracture risk,” he wrote.

“It is unlikely that the fracture risk question can be answered due to ethical limitations, but finding the best option, [whether it is] oral or intravenous bisphosphonate, timing, dose, and frequency, to minimize bone loss and the rebound increase in bone resorption after stopping long-term denosumab requires larger and longer studies of better design.”

The authors had no disclosures to report. Watts has been an investigator, consultant, and speaker for Amgen outside of the published editorial. Hofbauer is on advisory boards for Alexion Pharmaceuticals, Amolyt Pharma, Amgen, and UCB. Langdahl has been a primary investigator on previous and ongoing clinical trials involving denosumab.

A version of this article appeared on Medscape.com.

Patients who discontinue treatment with the osteoporosis drug denosumab, despite transitioning to zoledronate, show significant losses in lumbar spine bone mineral density (BMD) within a year, according to the latest findings to show that the rapid rebound of bone loss after denosumab discontinuation is not easily prevented with other therapies — even bisphosphonates.

“When initiating denosumab for osteoporosis treatment, it is recommended to engage in thorough shared decision-making with the patient to ensure they understand the potential risks associated with discontinuing the medication,” senior author Shau-Huai Fu, MD, PhD, Department of Orthopedics, National Taiwan University Hospital Yunlin Branch, Douliu, told this news organization.

Furthermore, “integrating a case manager system is crucial to support long-term adherence and compliance,” he added.

The results are from the Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial, published online in JAMA Network Open.

In the study, 101 patients were recruited between April 2019 and May 2021 at a referral center and two hospitals in Taiwan. The patients, including postmenopausal women and men over the age of 50, had been treated with regular denosumab for at least 2 years and had no previous exposure to other anti-osteoporosis medication.

They were randomized to treatment either with continuous denosumab at the standard dose of 60 mg twice yearly or to discontinue denosumab and receive the standard intravenous dose of the bisphosphonate zoledronate at 5 mg at the time when the next dose of denosumab would have been administered.

There were no differences between the two groups in serum bone turnover markers at baseline.

The current results, reflecting the first year of the 2-year study, show that, overall, those receiving zoledronate (n = 76), had a significant decrease in lumbar spine BMD, compared with a slight increase in the denosumab continuation group (–0.68% vs 1.30%, respectively; P = .03).

No significant differences were observed between the groups in terms of the study’s other measures of total hip BMD (median, 0% vs 1.12%; P = .24), and femoral neck BMD (median, 0.18% vs 0.17%; P = .71).

Additional findings from multivariable analyses in the study also supported results from previous studies showing that a longer duration of denosumab use is associated with a more substantial rebound effect: Among 15 of the denosumab users in the study who had ≥ 3 prior years of the drug, the reduction in lumbar spine BMD was even greater with zoledronate compared with denosumab continuation (–3.20% vs 1.30%; P = .003).

Though the lack of losses in the other measures of total hip and femoral neck BMD may seem encouraging, evidence from the bulk of other studies suggests cautious interpretation of those findings, Fu said.

“Although our study did not observe a noticeable decline in total hip or femoral neck BMD, other randomized controlled trials with longer durations of denosumab use have reported significant reductions in these areas,” Fu said. “Therefore, it cannot be assumed that non-lumbar spine regions are entirely safe.”

 

Fracture Risk Is the Overriding Concern

Meanwhile, the loss of lumbar spine BMD is of particular concern because of its role in what amounts to the broader, overriding concern of denosumab discontinuation — the risk for fracture, Fu noted.

“Real-world observations indicate that fractures caused by or associated with discontinuation of denosumab primarily occur in the spine,” he explained.

Previous research underscores the risk for fracture with denosumab discontinuation — and the greater risk with longer-term denosumab use, showing an 11.8% annual incidence of vertebral fracture after discontinuation of denosumab used for less than 2 years, increasing to 16.0% upon discontinuation after more than 2 years of treatment.

Randomized trials have shown sequential zoledronate to have some benefit in offsetting that risk, reducing first-year fracture risk by 3%-4% in some studies.

In the current study, 3 of 76 participants experienced a vertebral fracture in the first year of discontinuation, all involving women, including 2 who had been receiving denosumab for ≥ 4 years before medication transition.

If a transition to a bisphosphonate is anticipated, the collective findings suggest doing it as early on in denosumab treatment as possible, Fu and his colleagues noted in the study.

“When medication transition from denosumab is expected or when long-term denosumab treatment may not be suitable, earlier medication transition with potent sequential therapy should be considered,” they wrote.

 

Dosing Adjustments?

The findings add to the evidence that “patients who gain the most with denosumab are likely to lose the most with zoledronate,” Nelson Watts, MD, who authored an editorial accompanying the study, told this news organization.

Furthermore, “denosumab and other medications seem to do more [and faster] for BMD in the spine, so we expect more loss in the spine than in the hip,” said Watts, who is director of Mercy Health Osteoporosis and Bone Health Services, Bon Secours Mercy Health in Cincinnati, Ohio.

“Studies are needed but not yet done to see if a higher dose or more frequent zoledronate would be better for BMD than the ‘usual’ yearly dose,” Watts added.

The only published clinical recommendations on the matter are discussed in a position paper from the European Calcified Tissue Society (ECTS).

“Pending additional robust data, a pragmatic approach is to begin treatment with zoledronate 6 months after the last denosumab injection and monitor the effect with bone turnover markers, for example, 3 and 6 months after the zoledronate infusion,” they recommended.

In cases of increased bone turnover markers, including above the mean found in age- and sex-matched cohorts, “repeated infusion of zoledronate should be considered,” the society added.

If bone turnover markers are not available for monitoring the patients, “a pragmatic approach could be administrating a second infusion of zoledronate 6 months after the first infusion,” they wrote.

 

Clinicians Need to Be Proactive From the Start

Bente Langdahl, MD, of the Medical Department of Endocrinology, Aarhus University Hospital in Denmark, who was a coauthor on the ECTS position statement, told this news organization that clinicians should also be proactive on the other side of treatment — before it begins — to prevent problems with discontinuation.

“I think denosumab is a very good treatment for some patients with high fracture risk and very low BMD, but both patients and clinicians should know that this treatment is either lifelong or there needs to be a plan for discontinuation,” Langdahl said.

Langdahl noted that denosumab is coming off patent soon; hence, issues with cost could become more manageable.

But until then, “I think [cost] should be considered before starting treatment because if patients cannot afford denosumab, they should have been started on zoledronate from the beginning.”

 

Discontinuation Reasons Vary

Research indicates that, broadly, adherence to denosumab ranges from about 45% to 72% at 2 years, with some reasons for discontinuation including the need for dental treatment or cost, Fu and colleagues reported.

Fu added, however, that other reasons for discontinuing denosumab “are not due to ‘need’ but rather factors such as relocating, missing follow-up appointments, or poor adherence.”

Lorenz Hofbauer, MD, who is head of the Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III at the Technical University Medical Center in Dresden, Germany, noted that another issue contributing to some hesitation by patients about remaining on, or even initiating denosumab, is the known risk for osteonecrosis of the jaw (ONJ).

Though reported as being rare, research continuing to stir concern for ONJ with denosumab use includes one recent study of patients with breast cancer showing those treated with denosumab had a fivefold higher risk for ONJ vs those on bisphosphonates.

“About 20% of my patients have ONJ concerns or other questions, which may delay treatment with denosumab or other therapies,” Hofbauer told this news organization.

“There is a high need to discuss risk versus benefits toward a shared decision-making,” he said.

Conversely, however, Hofbauer noted that adherence to denosumab at his center is fairly high — at 90%, which he says is largely credited to an electronically supported recall system in place at the center.

Denosumab maker Amgen also offers patient reminders via email, text, or phone through its Bone Matters patient support system, which also provides access to a call center for questions or to update treatment appointment information.

In terms of the ongoing question of how to best prevent fracture risk when patients do wind up discontinuing denosumab, Watts concluded in his editorial that more robust studies are needed.

“The dilemma is what to do with longer-term users who stop, and the real question is not what happens to BMD, but what happens to fracture risk,” he wrote.

“It is unlikely that the fracture risk question can be answered due to ethical limitations, but finding the best option, [whether it is] oral or intravenous bisphosphonate, timing, dose, and frequency, to minimize bone loss and the rebound increase in bone resorption after stopping long-term denosumab requires larger and longer studies of better design.”

The authors had no disclosures to report. Watts has been an investigator, consultant, and speaker for Amgen outside of the published editorial. Hofbauer is on advisory boards for Alexion Pharmaceuticals, Amolyt Pharma, Amgen, and UCB. Langdahl has been a primary investigator on previous and ongoing clinical trials involving denosumab.

A version of this article appeared on Medscape.com.

Muvalaplin, a novel oral medication, safely and effectively lowers high levels of lipoprotein(a), or Lp(a), results from the phase 2 KRAKEN trial show.

Concentrations of Lp(a) cholesterol are genetically determined and remain steady throughout life. Levels of 125 nmol/L or higher promote clotting and inflammation, significantly increasing the risk for heart attack, stroke, aortic stenosis, and peripheral artery disease. This affects about 20% of the population, particularly people of Black African and South Asian descent.

There are currently no approved therapies that lower Lp(a), said study author Stephen Nicholls, MBBS, PhD, director of the Victorian Heart Institute at Monash University in Melbourne, Australia. Several injectable therapies are currently in clinical trials, but muvalaplin is the only oral option. The new drug lowers Lp(a) levels by disrupting the bond between the two parts of the Lp(a) particle.

 

The KRAKEN Trial

In the KRAKEN trial, 233 adults from around the world with very high Lp(a) levels (> 175 nmol/L) were randomized either to one of three daily doses of muvalaplin — 10, 60, or 240 mg — or to placebo for 12 weeks.

The researchers measured Lp(a) levels with a standard blood test and with a novel test designed to specifically measure levels of intact Lp(a) particles in the blood. In addition to Lp(a), the standard test detects one of its components, apolipoprotein A particles, that are bound to the drug, which can lead to an underestimation of Lp(a) reductions.

Lp(a) levels were up to 70.0% lower in the muvalaplin group than in the placebo group when measured with the traditional blood test and by up to 85.5% lower when measured with the new test. Approximately 82% of participants achieved an Lp(a) level lower than 125 nmol/L when measured with the traditional blood test, and 97% achieved that level when the new test was used. Patients who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, which were greater than the reductions seen in the 10 mg group. The drug was safe and generally well tolerated.

“This is a very reassuring phase 2 result,” Nicholls said when he presented the KRAKEN findings at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, which were simultaneously published online in JAMA. “It encourages the ongoing development of this agent.”

Lp(a) levels are not affected by changes in lifestyle or diet or by traditional lipid-lowering treatments like statins, said Erin Michos, MD, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved in the study.

And high Lp(a) levels confer significant cardiovascular risk even when other risks are reduced. So muvalaplin is “a highly promising approach to treat a previously untreatable disorder,” she explained.

Larger and longer studies, with more diverse patient populations, are needed to confirm the results and to determine whether reducing Lp(a) also improves cardiovascular outcomes, Michos pointed out.

“While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes,” Nicholls added.

A version of this article appeared on Medscape.com.

Muvalaplin, a novel oral medication, safely and effectively lowers high levels of lipoprotein(a), or Lp(a), results from the phase 2 KRAKEN trial show.

Concentrations of Lp(a) cholesterol are genetically determined and remain steady throughout life. Levels of 125 nmol/L or higher promote clotting and inflammation, significantly increasing the risk for heart attack, stroke, aortic stenosis, and peripheral artery disease. This affects about 20% of the population, particularly people of Black African and South Asian descent.

There are currently no approved therapies that lower Lp(a), said study author Stephen Nicholls, MBBS, PhD, director of the Victorian Heart Institute at Monash University in Melbourne, Australia. Several injectable therapies are currently in clinical trials, but muvalaplin is the only oral option. The new drug lowers Lp(a) levels by disrupting the bond between the two parts of the Lp(a) particle.

 

The KRAKEN Trial

In the KRAKEN trial, 233 adults from around the world with very high Lp(a) levels (> 175 nmol/L) were randomized either to one of three daily doses of muvalaplin — 10, 60, or 240 mg — or to placebo for 12 weeks.

The researchers measured Lp(a) levels with a standard blood test and with a novel test designed to specifically measure levels of intact Lp(a) particles in the blood. In addition to Lp(a), the standard test detects one of its components, apolipoprotein A particles, that are bound to the drug, which can lead to an underestimation of Lp(a) reductions.

Lp(a) levels were up to 70.0% lower in the muvalaplin group than in the placebo group when measured with the traditional blood test and by up to 85.5% lower when measured with the new test. Approximately 82% of participants achieved an Lp(a) level lower than 125 nmol/L when measured with the traditional blood test, and 97% achieved that level when the new test was used. Patients who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, which were greater than the reductions seen in the 10 mg group. The drug was safe and generally well tolerated.

“This is a very reassuring phase 2 result,” Nicholls said when he presented the KRAKEN findings at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, which were simultaneously published online in JAMA. “It encourages the ongoing development of this agent.”

Lp(a) levels are not affected by changes in lifestyle or diet or by traditional lipid-lowering treatments like statins, said Erin Michos, MD, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved in the study.

And high Lp(a) levels confer significant cardiovascular risk even when other risks are reduced. So muvalaplin is “a highly promising approach to treat a previously untreatable disorder,” she explained.

Larger and longer studies, with more diverse patient populations, are needed to confirm the results and to determine whether reducing Lp(a) also improves cardiovascular outcomes, Michos pointed out.

“While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes,” Nicholls added.

A version of this article appeared on Medscape.com.

Muvalaplin, a novel oral medication, safely and effectively lowers high levels of lipoprotein(a), or Lp(a), results from the phase 2 KRAKEN trial show.

Concentrations of Lp(a) cholesterol are genetically determined and remain steady throughout life. Levels of 125 nmol/L or higher promote clotting and inflammation, significantly increasing the risk for heart attack, stroke, aortic stenosis, and peripheral artery disease. This affects about 20% of the population, particularly people of Black African and South Asian descent.

There are currently no approved therapies that lower Lp(a), said study author Stephen Nicholls, MBBS, PhD, director of the Victorian Heart Institute at Monash University in Melbourne, Australia. Several injectable therapies are currently in clinical trials, but muvalaplin is the only oral option. The new drug lowers Lp(a) levels by disrupting the bond between the two parts of the Lp(a) particle.

 

The KRAKEN Trial

In the KRAKEN trial, 233 adults from around the world with very high Lp(a) levels (> 175 nmol/L) were randomized either to one of three daily doses of muvalaplin — 10, 60, or 240 mg — or to placebo for 12 weeks.

The researchers measured Lp(a) levels with a standard blood test and with a novel test designed to specifically measure levels of intact Lp(a) particles in the blood. In addition to Lp(a), the standard test detects one of its components, apolipoprotein A particles, that are bound to the drug, which can lead to an underestimation of Lp(a) reductions.

Lp(a) levels were up to 70.0% lower in the muvalaplin group than in the placebo group when measured with the traditional blood test and by up to 85.5% lower when measured with the new test. Approximately 82% of participants achieved an Lp(a) level lower than 125 nmol/L when measured with the traditional blood test, and 97% achieved that level when the new test was used. Patients who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, which were greater than the reductions seen in the 10 mg group. The drug was safe and generally well tolerated.

“This is a very reassuring phase 2 result,” Nicholls said when he presented the KRAKEN findings at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, which were simultaneously published online in JAMA. “It encourages the ongoing development of this agent.”

Lp(a) levels are not affected by changes in lifestyle or diet or by traditional lipid-lowering treatments like statins, said Erin Michos, MD, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved in the study.

And high Lp(a) levels confer significant cardiovascular risk even when other risks are reduced. So muvalaplin is “a highly promising approach to treat a previously untreatable disorder,” she explained.

Larger and longer studies, with more diverse patient populations, are needed to confirm the results and to determine whether reducing Lp(a) also improves cardiovascular outcomes, Michos pointed out.

“While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes,” Nicholls added.

A version of this article appeared on Medscape.com.

TOPLINE:

Light-intensity walking reduces postprandial glucose and diastolic blood pressure in young adults with obesity and can improve insulin levels, depending on the walking pattern.

METHODOLOGY:

• Researchers conducted a randomized crossover trial with 16 young adults aged 18-34 years with body mass index (BMI) ≥ 25 in Bangkok, Thailand, to examine the effects of different light-intensity walking patterns on postprandial cardiometabolic responses.
• Participants (mean age, 25; mean BMI, 29.8) engaged in four 7-hour experimental conditions, each involving a different activity: Uninterrupted sitting, 30-minutes of light-intensity walking, 3-minute light-intensity walking every 30 minutes, or a combination of both walking regimens. There was a 7- to 20-day washout period between each experiment period.
• Baseline and 6-hour postprandial concentrations of glucose, insulin, triglycerides, and blood pressure were measured.
• Incremental areas under the curve (iAUC) for each outcome and average blood pressure were compared between sitting and walking conditions.

TAKEAWAY:

• All the walking interventions reduced postprandial glucose concentrations and diastolic blood pressure compared with uninterrupted sitting.
• Continuous 30-minute light-intensity walking alone or combined with brief 3-minute bouts also attenuated postprandial insulin concentrations.
• No significant differences were found for triglycerides iAUC and systolic blood pressure between the four experiment conditions.

IN PRACTICE:

“These findings support the notion that engaging in light-intensity walking, regardless of the pattern, provides benefits to glycemic control. Moreover, the timing and patterns of light-intensity physical activity may be an important factor in reducing postprandial insulin concentrations,” the authors wrote.

SOURCE:

The study, led by Waris Wongpipit, PhD, Division of Health and Physical Education, Chulalongkorn University in Bangkok, Thailand, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s small sample size of 16 participants may limit the generalizability of the findings. The short duration of the study (7-hour experimental conditions) may not reflect long-term effects. The prescribed activities and dietary profiles, along with the controlled laboratory setting, may not accurately represent real-world conditions. The lack of objective physical activity/sedentary behavior measurement to confirm compliance between conditions is a limitation.

DISCLOSURES:

This study was supported by grants from the Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation, Thailand Science Research and Innovation, and Chulalongkorn University. Wongpipit received grant support from these organizations. Paddy C. Dempsey is supported by a National Health and Medical Research Council of Australia research fellowship. The other authors had no disclosures.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Light-intensity walking reduces postprandial glucose and diastolic blood pressure in young adults with obesity and can improve insulin levels, depending on the walking pattern.

METHODOLOGY:

• Researchers conducted a randomized crossover trial with 16 young adults aged 18-34 years with body mass index (BMI) ≥ 25 in Bangkok, Thailand, to examine the effects of different light-intensity walking patterns on postprandial cardiometabolic responses.
• Participants (mean age, 25; mean BMI, 29.8) engaged in four 7-hour experimental conditions, each involving a different activity: Uninterrupted sitting, 30-minutes of light-intensity walking, 3-minute light-intensity walking every 30 minutes, or a combination of both walking regimens. There was a 7- to 20-day washout period between each experiment period.
• Baseline and 6-hour postprandial concentrations of glucose, insulin, triglycerides, and blood pressure were measured.
• Incremental areas under the curve (iAUC) for each outcome and average blood pressure were compared between sitting and walking conditions.

TAKEAWAY:

• All the walking interventions reduced postprandial glucose concentrations and diastolic blood pressure compared with uninterrupted sitting.
• Continuous 30-minute light-intensity walking alone or combined with brief 3-minute bouts also attenuated postprandial insulin concentrations.
• No significant differences were found for triglycerides iAUC and systolic blood pressure between the four experiment conditions.

IN PRACTICE:

“These findings support the notion that engaging in light-intensity walking, regardless of the pattern, provides benefits to glycemic control. Moreover, the timing and patterns of light-intensity physical activity may be an important factor in reducing postprandial insulin concentrations,” the authors wrote.

SOURCE:

The study, led by Waris Wongpipit, PhD, Division of Health and Physical Education, Chulalongkorn University in Bangkok, Thailand, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s small sample size of 16 participants may limit the generalizability of the findings. The short duration of the study (7-hour experimental conditions) may not reflect long-term effects. The prescribed activities and dietary profiles, along with the controlled laboratory setting, may not accurately represent real-world conditions. The lack of objective physical activity/sedentary behavior measurement to confirm compliance between conditions is a limitation.

DISCLOSURES:

This study was supported by grants from the Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation, Thailand Science Research and Innovation, and Chulalongkorn University. Wongpipit received grant support from these organizations. Paddy C. Dempsey is supported by a National Health and Medical Research Council of Australia research fellowship. The other authors had no disclosures.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Light-intensity walking reduces postprandial glucose and diastolic blood pressure in young adults with obesity and can improve insulin levels, depending on the walking pattern.

METHODOLOGY:

• Researchers conducted a randomized crossover trial with 16 young adults aged 18-34 years with body mass index (BMI) ≥ 25 in Bangkok, Thailand, to examine the effects of different light-intensity walking patterns on postprandial cardiometabolic responses.
• Participants (mean age, 25; mean BMI, 29.8) engaged in four 7-hour experimental conditions, each involving a different activity: Uninterrupted sitting, 30-minutes of light-intensity walking, 3-minute light-intensity walking every 30 minutes, or a combination of both walking regimens. There was a 7- to 20-day washout period between each experiment period.
• Baseline and 6-hour postprandial concentrations of glucose, insulin, triglycerides, and blood pressure were measured.
• Incremental areas under the curve (iAUC) for each outcome and average blood pressure were compared between sitting and walking conditions.

TAKEAWAY:

• All the walking interventions reduced postprandial glucose concentrations and diastolic blood pressure compared with uninterrupted sitting.
• Continuous 30-minute light-intensity walking alone or combined with brief 3-minute bouts also attenuated postprandial insulin concentrations.
• No significant differences were found for triglycerides iAUC and systolic blood pressure between the four experiment conditions.

IN PRACTICE:

“These findings support the notion that engaging in light-intensity walking, regardless of the pattern, provides benefits to glycemic control. Moreover, the timing and patterns of light-intensity physical activity may be an important factor in reducing postprandial insulin concentrations,” the authors wrote.

SOURCE:

The study, led by Waris Wongpipit, PhD, Division of Health and Physical Education, Chulalongkorn University in Bangkok, Thailand, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s small sample size of 16 participants may limit the generalizability of the findings. The short duration of the study (7-hour experimental conditions) may not reflect long-term effects. The prescribed activities and dietary profiles, along with the controlled laboratory setting, may not accurately represent real-world conditions. The lack of objective physical activity/sedentary behavior measurement to confirm compliance between conditions is a limitation.

DISCLOSURES:

This study was supported by grants from the Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation, Thailand Science Research and Innovation, and Chulalongkorn University. Wongpipit received grant support from these organizations. Paddy C. Dempsey is supported by a National Health and Medical Research Council of Australia research fellowship. The other authors had no disclosures.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.