Pharmacology

NEW ORLEANS – Treatment of people with obesity but no diabetes with the dual–incretin agonist tirzepatide safely produced “unprecedented” levels of weight loss in the vast majority of patients in SURMOUNT-1, a placebo-controlled trial with more than 2,500 people with obesity or overweight plus at least one weight-related complication.

Although the pivotal trial did not directly compare weekly subcutaneous injection with the twincretin tirzepatide (at 5 mg, 10 mg, or 15 mg) with either bariatric surgery or what has been the reigning champ of weight-loss agents, a 2.4-mg/week injection of semaglutide (Wegovy), the new findings are impressive because they eclipsed semaglutide’s past performance in at least three important ways, said Ania M. Jastreboff, MD, PhD, SURMOUNT-1’s lead investigator, at the annual scientific sessions of the American Diabetes Association.

First, the highest-tested dosage of tirzepatide, 15 mg/week, for 72 weeks, produced a 5% or greater loss in baseline weight in 91%-96% of patients, an effect “not previously seen” in any prior phase 3 trial of a weight-loss agent, noted Dr. Jastreboff, an endocrinologist and director of Weight Management & Obesity Prevention at Yale University in New Haven, Conn.

Second, the average level of weight loss among the 630 people who received 15 mg/week was 22.5% in the on-treatment analysis, and 20.9% in the intention-to-treat analysis, again a magnitude of effect never before seen with any other medical intervention.

And in an exploratory analysis, 40% of people who received the highest-tested tirzepatide dose of 15 mg/week had at least a 25% loss in baseline weight in the on-treatment analysis, another example of unprecedented weight-loss achievement, said Dr. Jastreboff.

Looking at the data another way, the average baseline weight of those in the trial was 104 kg (230 lb) at the start, and the average weight loss was between 35 and 52 lbs by 72 weeks on treatment, Dr. Jastreboff said in a press conference. 

She noted, however, that not everyone will respond to tirzepatide, “but if you do respond to this medicine, you will feel full earlier, you won’t want to go back for seconds, and you may eat smaller amounts more often.”  

Such weight-loss agents will need to be taken chronically, in the same way that medications are for hypertension or dyslipidemia, Dr. Jastreboff stressed. “If you stop the antiobesity medication then the body fat mass set point will go back up so this necessitates long-term treatment.”

A new era: Weight loss ‘in the range of bariatric surgery’

Tirzepatide, developed by Lilly, has recently been approved in the United States for the treatment of type 2 diabetes, under the brand name Mounjaro.

SURMOUNT-1 was designed to examine the effect of the agent in overweight/obesity, and the company will be filing for the additional indication of weight loss in the future. Top-line results of SURMOUNT-1 generated much excitement when Lilly reported them back in April, including a story in The New York Times. 

Semaglutide, a Novo Nordisk drug, is approved in the United States for type 2 diabetes (as Ozempic at doses of either 1 mg or 2 mg per week) and also for weight loss, as Wegovy, at the higher dose of 2.4 mg per week. When Wegovy was given the green light by the Food and Drug Administration a year ago, it too was hailed as a “game changer” for obesity.

The weight-loss results seen in SURMOUNT-1 “put tirzepatide squarely in the range of weight loss achieved with bariatric surgery,” concluded Louis J. Aronne, MD, a coinvestigator on the trial, professor at Weill-Cornell Medicine in New York, and director of the Center for Weight Management and Metabolic Clinical Research of Weill-Cornell.

The results are “amazing,” and propel the weight-loss field into “a new era of obesity treatment,” commented Lee M. Kaplan, MD, who was not involved in the study and served as designated discussant for the trial.

Despite the lack of direct comparison, the findings indicate that “tirzepatide causes more weight loss than semaglutide,” and it provides “an opportunity to meet or exceed” the weight-loss effects of bariatric surgery, added Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

Simultaneously with Dr. Jastreboff’s report at the meeting, the results were published online in The New England Journal of Medicine.

An accompanying editorial agrees with Dr. Kaplan: “It is remarkable that the magnitude of weight loss with tirzepatide was similar to that with gastric bypass, which raises the potential for alternative medical approaches to the treatment of obesity.”

“The tides are shifting, and there are now more options for people with obesity to lose weight,” write Clifford J. Rosen, MD, of Tufts University, Boston, and Julie R. Ingelfinger, MD, of Harvard University and Massachusetts General Hospital, Boston.

Dual incretin agonism ‘enhances activity,’ says expert

Tirzepatide is the first agent on the U.S. market from a novel class of dual-incretin agonists, with a molecular structure engineered to activate both the glucagonlike protein-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP), the two predominant incretins in the human gut. This combined activity has led to the twincretin nickname for tirzepatide.

Semaglutide is a single-incretin agonist, with its activity focused exclusively on the GLP-1 receptor.

Dr. Aronne tied the apparently superior efficacy of tirzepatide relative to semaglutide directly to the added incretin activity of tirzepatide. “The dual approach enhances efficacy,” he proposed during his presentation at the meeting.

The impressive efficacy and reassuring safety profile reported from SURMOUNT-1 opens the door to a new approach to treating obesity, which in the past has often taken a back seat to treatments for dyslipidemia, hypertension, and diabetes.

“Now that we can treat obesity safely and effectively, it makes sense to treat obesity first,” Dr. Aronne recommended.

Dr. Jastreboff agreed: “Perhaps we can prevent diabetes by treating obesity head-on,” she remarked. 

Weight-loss agents gain U.S. traction

There have been concerns about patient access to these newer weight-loss drugs in the United States, given that the retail cost of semaglutide for obesity exceeds $1,000/month, but Dr. Aronne reported data that painted a more optimistic picture.

His numbers showed that during the first months that semaglutide was on the U.S. market as a weight-loss agent, the number of U.S. prescriptions written for branded antiobesity medications roughly doubled, a spike that seemed mostly driven by the introduction and growing use of semaglutide.

With tirzepatide, every prespecified cardiometabolic parameter assessed in the trial showed clinically meaningful improvements, reported Dr. Jastreboff, including an average 17% reduction in waist circumference in patients on either of the highest two dosages, a 34% average drop in total fat mass, an average 0.5–percentage point cut in baseline hemoglobin A1c at the highest two dosages, substantial cuts in fasting plasma glucose and fasting insulin levels,  an average 28% drop in triglyceride levels, and an average systolic blood pressure reduction of about 8 mm Hg that occurred within 24 weeks on treatment.

“I think that insurers will sign up” for tirzepatide coverage based on benefits like this, Dr. Aronne predicted.

SURMOUNT-1 randomized 2,539 patients with obesity or with overweight plus at least one weight-related complication at any of 119 sites in nine countries. They had a body mass index of 30 kg/m² or more, or 27 kg/m² or more and at least one weight-related complication, excluding diabetes. They were randomized in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period.

The study’s two primary endpoints were the average percentage change in body weight from entry to 72 weeks, and the percentage of participants reaching at least a 5% reduction in their baseline body weight by 72 weeks.

The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively

The trial ran from December 2019 to April 2022, so during the peak of the COVID-19 pandemic, which Dr. Jastreboff described as an “amazing feat.”

Jamy Ard, MD, who chaired the SURMOUNT-1 session quipped, after hearing the results, “Wow; that’s exciting. If you’re not excited by the results, you’d better check your pulse.”

Dr. Ard is a professor at Wake Forest University, Winston-Salem, N.C., and codirector of the Wake Forest Baptist Health Weight Management Center in Winston-Salem.

SURMOUNT-1 was sponsored by Eli Lilly, the company that markets tirzepatide (Mounjaro). Dr. Jastreboff has been an advisor or consultant to Eli Lilly, as well as to Boehringer Ingelheim, Intellihealth, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, Scholar Rock, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Aronne has been a consultant or advisor to, speaker on behalf of, or received research funding from Eli Lilly as well as from Altimmune, Amgen, Allurion, Intellihealth, Janssen, Novo Nordisk, Pfizer, and United Health group; he has an ownership interest in ERX, Gelesis, and Intellihealth; and he serves on the board of ERX, Jamieson Wellness, and Intellihealth. Dr. Kaplan has been a consultant to Eli Lilly, as well as to Amgen, Boehringer Ingelheim, Gelesis, Gilead, Novo Nordisk, Optum Health, Pfizer, Rhythm Pharmaceuticals, the Obesity and Nutrition Institute, and Xeno Biosciences. Dr. Ard has been a consultant to Eli Lilly, as well as to Nestle Health Sciences and Novo Nordisk, and he has received research funding from Boehringer Ingelheim, Epitomee, Medical, and United Health Group.

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

NEW ORLEANS – Treatment of people with obesity but no diabetes with the dual–incretin agonist tirzepatide safely produced “unprecedented” levels of weight loss in the vast majority of patients in SURMOUNT-1, a placebo-controlled trial with more than 2,500 people with obesity or overweight plus at least one weight-related complication.

Although the pivotal trial did not directly compare weekly subcutaneous injection with the twincretin tirzepatide (at 5 mg, 10 mg, or 15 mg) with either bariatric surgery or what has been the reigning champ of weight-loss agents, a 2.4-mg/week injection of semaglutide (Wegovy), the new findings are impressive because they eclipsed semaglutide’s past performance in at least three important ways, said Ania M. Jastreboff, MD, PhD, SURMOUNT-1’s lead investigator, at the annual scientific sessions of the American Diabetes Association.

First, the highest-tested dosage of tirzepatide, 15 mg/week, for 72 weeks, produced a 5% or greater loss in baseline weight in 91%-96% of patients, an effect “not previously seen” in any prior phase 3 trial of a weight-loss agent, noted Dr. Jastreboff, an endocrinologist and director of Weight Management & Obesity Prevention at Yale University in New Haven, Conn.

Second, the average level of weight loss among the 630 people who received 15 mg/week was 22.5% in the on-treatment analysis, and 20.9% in the intention-to-treat analysis, again a magnitude of effect never before seen with any other medical intervention.

And in an exploratory analysis, 40% of people who received the highest-tested tirzepatide dose of 15 mg/week had at least a 25% loss in baseline weight in the on-treatment analysis, another example of unprecedented weight-loss achievement, said Dr. Jastreboff.

Looking at the data another way, the average baseline weight of those in the trial was 104 kg (230 lb) at the start, and the average weight loss was between 35 and 52 lbs by 72 weeks on treatment, Dr. Jastreboff said in a press conference. 

She noted, however, that not everyone will respond to tirzepatide, “but if you do respond to this medicine, you will feel full earlier, you won’t want to go back for seconds, and you may eat smaller amounts more often.”  

Such weight-loss agents will need to be taken chronically, in the same way that medications are for hypertension or dyslipidemia, Dr. Jastreboff stressed. “If you stop the antiobesity medication then the body fat mass set point will go back up so this necessitates long-term treatment.”

A new era: Weight loss ‘in the range of bariatric surgery’

Tirzepatide, developed by Lilly, has recently been approved in the United States for the treatment of type 2 diabetes, under the brand name Mounjaro.

SURMOUNT-1 was designed to examine the effect of the agent in overweight/obesity, and the company will be filing for the additional indication of weight loss in the future. Top-line results of SURMOUNT-1 generated much excitement when Lilly reported them back in April, including a story in The New York Times. 

Semaglutide, a Novo Nordisk drug, is approved in the United States for type 2 diabetes (as Ozempic at doses of either 1 mg or 2 mg per week) and also for weight loss, as Wegovy, at the higher dose of 2.4 mg per week. When Wegovy was given the green light by the Food and Drug Administration a year ago, it too was hailed as a “game changer” for obesity.

The weight-loss results seen in SURMOUNT-1 “put tirzepatide squarely in the range of weight loss achieved with bariatric surgery,” concluded Louis J. Aronne, MD, a coinvestigator on the trial, professor at Weill-Cornell Medicine in New York, and director of the Center for Weight Management and Metabolic Clinical Research of Weill-Cornell.

The results are “amazing,” and propel the weight-loss field into “a new era of obesity treatment,” commented Lee M. Kaplan, MD, who was not involved in the study and served as designated discussant for the trial.

Despite the lack of direct comparison, the findings indicate that “tirzepatide causes more weight loss than semaglutide,” and it provides “an opportunity to meet or exceed” the weight-loss effects of bariatric surgery, added Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

Simultaneously with Dr. Jastreboff’s report at the meeting, the results were published online in The New England Journal of Medicine.

An accompanying editorial agrees with Dr. Kaplan: “It is remarkable that the magnitude of weight loss with tirzepatide was similar to that with gastric bypass, which raises the potential for alternative medical approaches to the treatment of obesity.”

“The tides are shifting, and there are now more options for people with obesity to lose weight,” write Clifford J. Rosen, MD, of Tufts University, Boston, and Julie R. Ingelfinger, MD, of Harvard University and Massachusetts General Hospital, Boston.

Dual incretin agonism ‘enhances activity,’ says expert

Tirzepatide is the first agent on the U.S. market from a novel class of dual-incretin agonists, with a molecular structure engineered to activate both the glucagonlike protein-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP), the two predominant incretins in the human gut. This combined activity has led to the twincretin nickname for tirzepatide.

Semaglutide is a single-incretin agonist, with its activity focused exclusively on the GLP-1 receptor.

Dr. Aronne tied the apparently superior efficacy of tirzepatide relative to semaglutide directly to the added incretin activity of tirzepatide. “The dual approach enhances efficacy,” he proposed during his presentation at the meeting.

The impressive efficacy and reassuring safety profile reported from SURMOUNT-1 opens the door to a new approach to treating obesity, which in the past has often taken a back seat to treatments for dyslipidemia, hypertension, and diabetes.

“Now that we can treat obesity safely and effectively, it makes sense to treat obesity first,” Dr. Aronne recommended.

Dr. Jastreboff agreed: “Perhaps we can prevent diabetes by treating obesity head-on,” she remarked. 

Weight-loss agents gain U.S. traction

There have been concerns about patient access to these newer weight-loss drugs in the United States, given that the retail cost of semaglutide for obesity exceeds $1,000/month, but Dr. Aronne reported data that painted a more optimistic picture.

His numbers showed that during the first months that semaglutide was on the U.S. market as a weight-loss agent, the number of U.S. prescriptions written for branded antiobesity medications roughly doubled, a spike that seemed mostly driven by the introduction and growing use of semaglutide.

With tirzepatide, every prespecified cardiometabolic parameter assessed in the trial showed clinically meaningful improvements, reported Dr. Jastreboff, including an average 17% reduction in waist circumference in patients on either of the highest two dosages, a 34% average drop in total fat mass, an average 0.5–percentage point cut in baseline hemoglobin A1c at the highest two dosages, substantial cuts in fasting plasma glucose and fasting insulin levels,  an average 28% drop in triglyceride levels, and an average systolic blood pressure reduction of about 8 mm Hg that occurred within 24 weeks on treatment.

“I think that insurers will sign up” for tirzepatide coverage based on benefits like this, Dr. Aronne predicted.

SURMOUNT-1 randomized 2,539 patients with obesity or with overweight plus at least one weight-related complication at any of 119 sites in nine countries. They had a body mass index of 30 kg/m² or more, or 27 kg/m² or more and at least one weight-related complication, excluding diabetes. They were randomized in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period.

The study’s two primary endpoints were the average percentage change in body weight from entry to 72 weeks, and the percentage of participants reaching at least a 5% reduction in their baseline body weight by 72 weeks.

The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively

The trial ran from December 2019 to April 2022, so during the peak of the COVID-19 pandemic, which Dr. Jastreboff described as an “amazing feat.”

Jamy Ard, MD, who chaired the SURMOUNT-1 session quipped, after hearing the results, “Wow; that’s exciting. If you’re not excited by the results, you’d better check your pulse.”

Dr. Ard is a professor at Wake Forest University, Winston-Salem, N.C., and codirector of the Wake Forest Baptist Health Weight Management Center in Winston-Salem.

SURMOUNT-1 was sponsored by Eli Lilly, the company that markets tirzepatide (Mounjaro). Dr. Jastreboff has been an advisor or consultant to Eli Lilly, as well as to Boehringer Ingelheim, Intellihealth, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, Scholar Rock, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Aronne has been a consultant or advisor to, speaker on behalf of, or received research funding from Eli Lilly as well as from Altimmune, Amgen, Allurion, Intellihealth, Janssen, Novo Nordisk, Pfizer, and United Health group; he has an ownership interest in ERX, Gelesis, and Intellihealth; and he serves on the board of ERX, Jamieson Wellness, and Intellihealth. Dr. Kaplan has been a consultant to Eli Lilly, as well as to Amgen, Boehringer Ingelheim, Gelesis, Gilead, Novo Nordisk, Optum Health, Pfizer, Rhythm Pharmaceuticals, the Obesity and Nutrition Institute, and Xeno Biosciences. Dr. Ard has been a consultant to Eli Lilly, as well as to Nestle Health Sciences and Novo Nordisk, and he has received research funding from Boehringer Ingelheim, Epitomee, Medical, and United Health Group.

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

NEW ORLEANS – Treatment of people with obesity but no diabetes with the dual–incretin agonist tirzepatide safely produced “unprecedented” levels of weight loss in the vast majority of patients in SURMOUNT-1, a placebo-controlled trial with more than 2,500 people with obesity or overweight plus at least one weight-related complication.

Although the pivotal trial did not directly compare weekly subcutaneous injection with the twincretin tirzepatide (at 5 mg, 10 mg, or 15 mg) with either bariatric surgery or what has been the reigning champ of weight-loss agents, a 2.4-mg/week injection of semaglutide (Wegovy), the new findings are impressive because they eclipsed semaglutide’s past performance in at least three important ways, said Ania M. Jastreboff, MD, PhD, SURMOUNT-1’s lead investigator, at the annual scientific sessions of the American Diabetes Association.

First, the highest-tested dosage of tirzepatide, 15 mg/week, for 72 weeks, produced a 5% or greater loss in baseline weight in 91%-96% of patients, an effect “not previously seen” in any prior phase 3 trial of a weight-loss agent, noted Dr. Jastreboff, an endocrinologist and director of Weight Management & Obesity Prevention at Yale University in New Haven, Conn.

Second, the average level of weight loss among the 630 people who received 15 mg/week was 22.5% in the on-treatment analysis, and 20.9% in the intention-to-treat analysis, again a magnitude of effect never before seen with any other medical intervention.

And in an exploratory analysis, 40% of people who received the highest-tested tirzepatide dose of 15 mg/week had at least a 25% loss in baseline weight in the on-treatment analysis, another example of unprecedented weight-loss achievement, said Dr. Jastreboff.

Looking at the data another way, the average baseline weight of those in the trial was 104 kg (230 lb) at the start, and the average weight loss was between 35 and 52 lbs by 72 weeks on treatment, Dr. Jastreboff said in a press conference. 

She noted, however, that not everyone will respond to tirzepatide, “but if you do respond to this medicine, you will feel full earlier, you won’t want to go back for seconds, and you may eat smaller amounts more often.”  

Such weight-loss agents will need to be taken chronically, in the same way that medications are for hypertension or dyslipidemia, Dr. Jastreboff stressed. “If you stop the antiobesity medication then the body fat mass set point will go back up so this necessitates long-term treatment.”

A new era: Weight loss ‘in the range of bariatric surgery’

Tirzepatide, developed by Lilly, has recently been approved in the United States for the treatment of type 2 diabetes, under the brand name Mounjaro.

SURMOUNT-1 was designed to examine the effect of the agent in overweight/obesity, and the company will be filing for the additional indication of weight loss in the future. Top-line results of SURMOUNT-1 generated much excitement when Lilly reported them back in April, including a story in The New York Times. 

Semaglutide, a Novo Nordisk drug, is approved in the United States for type 2 diabetes (as Ozempic at doses of either 1 mg or 2 mg per week) and also for weight loss, as Wegovy, at the higher dose of 2.4 mg per week. When Wegovy was given the green light by the Food and Drug Administration a year ago, it too was hailed as a “game changer” for obesity.

The weight-loss results seen in SURMOUNT-1 “put tirzepatide squarely in the range of weight loss achieved with bariatric surgery,” concluded Louis J. Aronne, MD, a coinvestigator on the trial, professor at Weill-Cornell Medicine in New York, and director of the Center for Weight Management and Metabolic Clinical Research of Weill-Cornell.

The results are “amazing,” and propel the weight-loss field into “a new era of obesity treatment,” commented Lee M. Kaplan, MD, who was not involved in the study and served as designated discussant for the trial.

Despite the lack of direct comparison, the findings indicate that “tirzepatide causes more weight loss than semaglutide,” and it provides “an opportunity to meet or exceed” the weight-loss effects of bariatric surgery, added Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

Simultaneously with Dr. Jastreboff’s report at the meeting, the results were published online in The New England Journal of Medicine.

An accompanying editorial agrees with Dr. Kaplan: “It is remarkable that the magnitude of weight loss with tirzepatide was similar to that with gastric bypass, which raises the potential for alternative medical approaches to the treatment of obesity.”

“The tides are shifting, and there are now more options for people with obesity to lose weight,” write Clifford J. Rosen, MD, of Tufts University, Boston, and Julie R. Ingelfinger, MD, of Harvard University and Massachusetts General Hospital, Boston.

Dual incretin agonism ‘enhances activity,’ says expert

Tirzepatide is the first agent on the U.S. market from a novel class of dual-incretin agonists, with a molecular structure engineered to activate both the glucagonlike protein-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP), the two predominant incretins in the human gut. This combined activity has led to the twincretin nickname for tirzepatide.

Semaglutide is a single-incretin agonist, with its activity focused exclusively on the GLP-1 receptor.

Dr. Aronne tied the apparently superior efficacy of tirzepatide relative to semaglutide directly to the added incretin activity of tirzepatide. “The dual approach enhances efficacy,” he proposed during his presentation at the meeting.

The impressive efficacy and reassuring safety profile reported from SURMOUNT-1 opens the door to a new approach to treating obesity, which in the past has often taken a back seat to treatments for dyslipidemia, hypertension, and diabetes.

“Now that we can treat obesity safely and effectively, it makes sense to treat obesity first,” Dr. Aronne recommended.

Dr. Jastreboff agreed: “Perhaps we can prevent diabetes by treating obesity head-on,” she remarked. 

Weight-loss agents gain U.S. traction

There have been concerns about patient access to these newer weight-loss drugs in the United States, given that the retail cost of semaglutide for obesity exceeds $1,000/month, but Dr. Aronne reported data that painted a more optimistic picture.

His numbers showed that during the first months that semaglutide was on the U.S. market as a weight-loss agent, the number of U.S. prescriptions written for branded antiobesity medications roughly doubled, a spike that seemed mostly driven by the introduction and growing use of semaglutide.

With tirzepatide, every prespecified cardiometabolic parameter assessed in the trial showed clinically meaningful improvements, reported Dr. Jastreboff, including an average 17% reduction in waist circumference in patients on either of the highest two dosages, a 34% average drop in total fat mass, an average 0.5–percentage point cut in baseline hemoglobin A1c at the highest two dosages, substantial cuts in fasting plasma glucose and fasting insulin levels,  an average 28% drop in triglyceride levels, and an average systolic blood pressure reduction of about 8 mm Hg that occurred within 24 weeks on treatment.

“I think that insurers will sign up” for tirzepatide coverage based on benefits like this, Dr. Aronne predicted.

SURMOUNT-1 randomized 2,539 patients with obesity or with overweight plus at least one weight-related complication at any of 119 sites in nine countries. They had a body mass index of 30 kg/m² or more, or 27 kg/m² or more and at least one weight-related complication, excluding diabetes. They were randomized in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period.

The study’s two primary endpoints were the average percentage change in body weight from entry to 72 weeks, and the percentage of participants reaching at least a 5% reduction in their baseline body weight by 72 weeks.

The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively

The trial ran from December 2019 to April 2022, so during the peak of the COVID-19 pandemic, which Dr. Jastreboff described as an “amazing feat.”

Jamy Ard, MD, who chaired the SURMOUNT-1 session quipped, after hearing the results, “Wow; that’s exciting. If you’re not excited by the results, you’d better check your pulse.”

Dr. Ard is a professor at Wake Forest University, Winston-Salem, N.C., and codirector of the Wake Forest Baptist Health Weight Management Center in Winston-Salem.

SURMOUNT-1 was sponsored by Eli Lilly, the company that markets tirzepatide (Mounjaro). Dr. Jastreboff has been an advisor or consultant to Eli Lilly, as well as to Boehringer Ingelheim, Intellihealth, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, Scholar Rock, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Aronne has been a consultant or advisor to, speaker on behalf of, or received research funding from Eli Lilly as well as from Altimmune, Amgen, Allurion, Intellihealth, Janssen, Novo Nordisk, Pfizer, and United Health group; he has an ownership interest in ERX, Gelesis, and Intellihealth; and he serves on the board of ERX, Jamieson Wellness, and Intellihealth. Dr. Kaplan has been a consultant to Eli Lilly, as well as to Amgen, Boehringer Ingelheim, Gelesis, Gilead, Novo Nordisk, Optum Health, Pfizer, Rhythm Pharmaceuticals, the Obesity and Nutrition Institute, and Xeno Biosciences. Dr. Ard has been a consultant to Eli Lilly, as well as to Nestle Health Sciences and Novo Nordisk, and he has received research funding from Boehringer Ingelheim, Epitomee, Medical, and United Health Group.

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

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

The number of general internists choosing a career in hospital medicine jumped from 25% to 40% over 10 years, according to data from the American Board of Internal Medicine.

In a new study, published in Annals of Internal Medicine, researchers from ABIM reviewed certification data from 67,902 general internists, accounting for 80% of all general internists certified in the United States from 1990 to 2017.

The researchers also used data from Medicare fee-for-service claims from 2008-2018 to measure and categorize practice setting types. The claims were from patients aged 65 years or older with at least 20 evaluation and management visits each year. Practice settings were categorized as hospitalist, outpatient, or mixed.

“ABIM is always working to understand the real-life experience of physicians, and this project grew out of that sort of analysis,” lead author Bradley M. Gray, PhD, a health services researcher at ABIM in Philadelphia, said in an interview. “We wanted to better understand practice setting, because that relates to the kinds of questions that we ask on our certifying exams. When we did this, we noticed a trend toward hospital medicine.”

Overall, the percentages of general internists in hospitalist practice and outpatient-only practice increased during the study period, from 25% to 40% and from 23% to 38%, respectively. By contrast, the percentage of general internists in a mixed-practice setting decreased from 52% to 23%, a 56% decline. Most of the physicians who left the mixed practice setting switched to outpatient-only practices.

Among the internists certified in 2017, 71% practiced as hospitalists, compared with 8% practicing as outpatient-only physicians. Most physicians remained in their original choice of practice setting. For physicians certified in 1999 and 2012, 86% and 85%, respectively, of those who chose hospitalist medicine remained in the hospital setting 5 years later, as did 95% of outpatient physicians, but only 57% of mixed-practice physicians.

The shift to outpatient practice among senior physicians offset the potential decline in outpatient primary care resulting from the increased choice of hospitalist medicine by new internists, the researchers noted.

The study findings were limited by several factors, including the reliance on Medicare fee-for-service claims, the researchers noted.

“We were surprised by both the dramatic shift toward hospital medicine by new physicians and the shift to outpatient only (an extreme category) for more senior physicians,” Dr. Gray said in an interview.

The shift toward outpatient practice among older physicians may be driven by convenience, said Dr. Gray. “I suspect that it is more efficient to specialize in terms of practice setting. Only seeing patients in the outpatient setting means that you don’t have to travel to the hospital, which can be time consuming.

“Also, with fewer new physicians going into primary care, older physicians need to focus on outpatient visits. This could be problematic in the future as more senior physicians retire and are replaced by new physicians who focus on hospital care,” which could lead to more shortages in primary care physicians, he explained.

The trend toward hospital medicine as a career has been going on since before the pandemic, said Dr. Gray. “I don’t think the pandemic will ultimately impact this trend. That said, at least in the short run, there may have been a decreased demand for primary care, but that is just my speculation. As more data flow in we will be able to answer this question more directly.”

Next steps for research included digging deeper into the data to understand the nature of conditions facing hospitalists, Dr. Gray said.
 

Implications for primary care

“This study provides an updated snapshot of the popularity of hospital medicine,” said Bradley A. Sharpe, MD, of the division of hospital medicine at the University of California, San Francisco. “It is also important to conduct this study now as health systems think about the challenge of providing high-quality primary care with a rapidly decreasing number of internists choosing to practice outpatient medicine.” Dr. Sharpe was not involved in the study.

“The most surprising finding to me was not the increase in general internists focusing on hospital medicine, but the amount of the increase; it is remarkable that nearly three quarters of general internists are choosing to practice as hospitalists,” Dr. Sharpe noted.

“I think there are a number of key factors at play,” he said. “First, as hospital medicine as a field is now more than 25 years old, hospitals and health systems have evolved to create hospital medicine jobs that are interesting, engaging, rewarding (financially and otherwise), doable, and sustainable. Second, being an outpatient internist is incredibly challenging; multiple studies have shown that it is essentially impossible to complete the evidence-based preventive care for a panel of patients on top of everything else. We know burnout rates are often higher among primary care and family medicine providers. On top of that, the expansion of electronic health records and patient access has led to a massive increase in messages to providers; this has been shown to be associated with burnout.”

The potential impact of the pandemic on physicians’ choices and the trend toward hospital medicine is an interested question, Dr. Sharpe said. The current study showed only trends through 2017.

“To be honest, I think it is difficult to predict,” he said. “Hospitalists shouldered much of the burden of COVID care nationally and burnout rates are high. One could imagine the extra work (as well as concern for personal safety) could lead to fewer providers choosing hospital medicine.

“At the same time, the pandemic has driven many of us to reflect on life and our values and what is important and, through that lens, providers might choose hospital medicine as a more sustainable, do-able, rewarding, and enjoyable career choice,” Dr. Sharpe emphasized.

“Additional research could explore the drivers of this clear trend toward hospital medicine. Determining what is motivating this trend could help hospitals and health systems ensure they have the right workforce for the future and, in particular, how to create outpatient positions that are attractive and rewarding,” he said.

The study received no outside funding. The researchers and Dr. Sharpe disclosed no relevant financial relationships.

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

The number of general internists choosing a career in hospital medicine jumped from 25% to 40% over 10 years, according to data from the American Board of Internal Medicine.

In a new study, published in Annals of Internal Medicine, researchers from ABIM reviewed certification data from 67,902 general internists, accounting for 80% of all general internists certified in the United States from 1990 to 2017.

The researchers also used data from Medicare fee-for-service claims from 2008-2018 to measure and categorize practice setting types. The claims were from patients aged 65 years or older with at least 20 evaluation and management visits each year. Practice settings were categorized as hospitalist, outpatient, or mixed.

“ABIM is always working to understand the real-life experience of physicians, and this project grew out of that sort of analysis,” lead author Bradley M. Gray, PhD, a health services researcher at ABIM in Philadelphia, said in an interview. “We wanted to better understand practice setting, because that relates to the kinds of questions that we ask on our certifying exams. When we did this, we noticed a trend toward hospital medicine.”

Overall, the percentages of general internists in hospitalist practice and outpatient-only practice increased during the study period, from 25% to 40% and from 23% to 38%, respectively. By contrast, the percentage of general internists in a mixed-practice setting decreased from 52% to 23%, a 56% decline. Most of the physicians who left the mixed practice setting switched to outpatient-only practices.

Among the internists certified in 2017, 71% practiced as hospitalists, compared with 8% practicing as outpatient-only physicians. Most physicians remained in their original choice of practice setting. For physicians certified in 1999 and 2012, 86% and 85%, respectively, of those who chose hospitalist medicine remained in the hospital setting 5 years later, as did 95% of outpatient physicians, but only 57% of mixed-practice physicians.

The shift to outpatient practice among senior physicians offset the potential decline in outpatient primary care resulting from the increased choice of hospitalist medicine by new internists, the researchers noted.

The study findings were limited by several factors, including the reliance on Medicare fee-for-service claims, the researchers noted.

“We were surprised by both the dramatic shift toward hospital medicine by new physicians and the shift to outpatient only (an extreme category) for more senior physicians,” Dr. Gray said in an interview.

The shift toward outpatient practice among older physicians may be driven by convenience, said Dr. Gray. “I suspect that it is more efficient to specialize in terms of practice setting. Only seeing patients in the outpatient setting means that you don’t have to travel to the hospital, which can be time consuming.

“Also, with fewer new physicians going into primary care, older physicians need to focus on outpatient visits. This could be problematic in the future as more senior physicians retire and are replaced by new physicians who focus on hospital care,” which could lead to more shortages in primary care physicians, he explained.

The trend toward hospital medicine as a career has been going on since before the pandemic, said Dr. Gray. “I don’t think the pandemic will ultimately impact this trend. That said, at least in the short run, there may have been a decreased demand for primary care, but that is just my speculation. As more data flow in we will be able to answer this question more directly.”

Next steps for research included digging deeper into the data to understand the nature of conditions facing hospitalists, Dr. Gray said.
 

Implications for primary care

“This study provides an updated snapshot of the popularity of hospital medicine,” said Bradley A. Sharpe, MD, of the division of hospital medicine at the University of California, San Francisco. “It is also important to conduct this study now as health systems think about the challenge of providing high-quality primary care with a rapidly decreasing number of internists choosing to practice outpatient medicine.” Dr. Sharpe was not involved in the study.

“The most surprising finding to me was not the increase in general internists focusing on hospital medicine, but the amount of the increase; it is remarkable that nearly three quarters of general internists are choosing to practice as hospitalists,” Dr. Sharpe noted.

“I think there are a number of key factors at play,” he said. “First, as hospital medicine as a field is now more than 25 years old, hospitals and health systems have evolved to create hospital medicine jobs that are interesting, engaging, rewarding (financially and otherwise), doable, and sustainable. Second, being an outpatient internist is incredibly challenging; multiple studies have shown that it is essentially impossible to complete the evidence-based preventive care for a panel of patients on top of everything else. We know burnout rates are often higher among primary care and family medicine providers. On top of that, the expansion of electronic health records and patient access has led to a massive increase in messages to providers; this has been shown to be associated with burnout.”

The potential impact of the pandemic on physicians’ choices and the trend toward hospital medicine is an interested question, Dr. Sharpe said. The current study showed only trends through 2017.

“To be honest, I think it is difficult to predict,” he said. “Hospitalists shouldered much of the burden of COVID care nationally and burnout rates are high. One could imagine the extra work (as well as concern for personal safety) could lead to fewer providers choosing hospital medicine.

“At the same time, the pandemic has driven many of us to reflect on life and our values and what is important and, through that lens, providers might choose hospital medicine as a more sustainable, do-able, rewarding, and enjoyable career choice,” Dr. Sharpe emphasized.

“Additional research could explore the drivers of this clear trend toward hospital medicine. Determining what is motivating this trend could help hospitals and health systems ensure they have the right workforce for the future and, in particular, how to create outpatient positions that are attractive and rewarding,” he said.

The study received no outside funding. The researchers and Dr. Sharpe disclosed no relevant financial relationships.

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

The number of general internists choosing a career in hospital medicine jumped from 25% to 40% over 10 years, according to data from the American Board of Internal Medicine.

In a new study, published in Annals of Internal Medicine, researchers from ABIM reviewed certification data from 67,902 general internists, accounting for 80% of all general internists certified in the United States from 1990 to 2017.

The researchers also used data from Medicare fee-for-service claims from 2008-2018 to measure and categorize practice setting types. The claims were from patients aged 65 years or older with at least 20 evaluation and management visits each year. Practice settings were categorized as hospitalist, outpatient, or mixed.

“ABIM is always working to understand the real-life experience of physicians, and this project grew out of that sort of analysis,” lead author Bradley M. Gray, PhD, a health services researcher at ABIM in Philadelphia, said in an interview. “We wanted to better understand practice setting, because that relates to the kinds of questions that we ask on our certifying exams. When we did this, we noticed a trend toward hospital medicine.”

Overall, the percentages of general internists in hospitalist practice and outpatient-only practice increased during the study period, from 25% to 40% and from 23% to 38%, respectively. By contrast, the percentage of general internists in a mixed-practice setting decreased from 52% to 23%, a 56% decline. Most of the physicians who left the mixed practice setting switched to outpatient-only practices.

Among the internists certified in 2017, 71% practiced as hospitalists, compared with 8% practicing as outpatient-only physicians. Most physicians remained in their original choice of practice setting. For physicians certified in 1999 and 2012, 86% and 85%, respectively, of those who chose hospitalist medicine remained in the hospital setting 5 years later, as did 95% of outpatient physicians, but only 57% of mixed-practice physicians.

The shift to outpatient practice among senior physicians offset the potential decline in outpatient primary care resulting from the increased choice of hospitalist medicine by new internists, the researchers noted.

The study findings were limited by several factors, including the reliance on Medicare fee-for-service claims, the researchers noted.

“We were surprised by both the dramatic shift toward hospital medicine by new physicians and the shift to outpatient only (an extreme category) for more senior physicians,” Dr. Gray said in an interview.

The shift toward outpatient practice among older physicians may be driven by convenience, said Dr. Gray. “I suspect that it is more efficient to specialize in terms of practice setting. Only seeing patients in the outpatient setting means that you don’t have to travel to the hospital, which can be time consuming.

“Also, with fewer new physicians going into primary care, older physicians need to focus on outpatient visits. This could be problematic in the future as more senior physicians retire and are replaced by new physicians who focus on hospital care,” which could lead to more shortages in primary care physicians, he explained.

The trend toward hospital medicine as a career has been going on since before the pandemic, said Dr. Gray. “I don’t think the pandemic will ultimately impact this trend. That said, at least in the short run, there may have been a decreased demand for primary care, but that is just my speculation. As more data flow in we will be able to answer this question more directly.”

Next steps for research included digging deeper into the data to understand the nature of conditions facing hospitalists, Dr. Gray said.
 

Implications for primary care

“This study provides an updated snapshot of the popularity of hospital medicine,” said Bradley A. Sharpe, MD, of the division of hospital medicine at the University of California, San Francisco. “It is also important to conduct this study now as health systems think about the challenge of providing high-quality primary care with a rapidly decreasing number of internists choosing to practice outpatient medicine.” Dr. Sharpe was not involved in the study.

“The most surprising finding to me was not the increase in general internists focusing on hospital medicine, but the amount of the increase; it is remarkable that nearly three quarters of general internists are choosing to practice as hospitalists,” Dr. Sharpe noted.

“I think there are a number of key factors at play,” he said. “First, as hospital medicine as a field is now more than 25 years old, hospitals and health systems have evolved to create hospital medicine jobs that are interesting, engaging, rewarding (financially and otherwise), doable, and sustainable. Second, being an outpatient internist is incredibly challenging; multiple studies have shown that it is essentially impossible to complete the evidence-based preventive care for a panel of patients on top of everything else. We know burnout rates are often higher among primary care and family medicine providers. On top of that, the expansion of electronic health records and patient access has led to a massive increase in messages to providers; this has been shown to be associated with burnout.”

The potential impact of the pandemic on physicians’ choices and the trend toward hospital medicine is an interested question, Dr. Sharpe said. The current study showed only trends through 2017.

“To be honest, I think it is difficult to predict,” he said. “Hospitalists shouldered much of the burden of COVID care nationally and burnout rates are high. One could imagine the extra work (as well as concern for personal safety) could lead to fewer providers choosing hospital medicine.

“At the same time, the pandemic has driven many of us to reflect on life and our values and what is important and, through that lens, providers might choose hospital medicine as a more sustainable, do-able, rewarding, and enjoyable career choice,” Dr. Sharpe emphasized.

“Additional research could explore the drivers of this clear trend toward hospital medicine. Determining what is motivating this trend could help hospitals and health systems ensure they have the right workforce for the future and, in particular, how to create outpatient positions that are attractive and rewarding,” he said.

The study received no outside funding. The researchers and Dr. Sharpe disclosed no relevant financial relationships.

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

MAR DEL PLATA, ARGENTINA – Psychiatrists should prescribe metformin early to patients who experience rapid weight gain after they begin taking antipsychotic drugs, according to a new evidence-based Irish guideline for the management of this common complication in adults with psychoses who are taking medications.

The document was discussed during one of the sessions of the XXXV Argentine Congress of Psychiatry of the Association of Argentine Psychiatrists. The document also was presented by one of its authors at the European Congress on Obesity 2022.

The guideline encourages psychiatrists not to underestimate the adverse metabolic effects of their treatments and encourages them to contemplate and carry out this prevention and management strategy, commented María Delia Michat, PhD, professor of clinical psychiatry and psychopharmacology at the APSA Postgraduate Training Institute, Buenos Aires.

“Although it is always good to work as a team, it is usually we psychiatrists who coordinate the pharmacological treatment of our patients, and we have to know how to manage drugs that can prevent cardiovascular disease,” Dr. Michat said in an interview.

“The new guideline is helpful because it protocolizes the use of metformin, which is the cheapest drug and has the most evidence for antipsychotic-induced weight gain,” she added.
 

Avoiding metabolic syndrome

In patients with schizophrenia, obesity rates are 40% higher than in the general population, and 80% of patients develop weight gain after their first treatment, noted Dr. Michat. “Right away, weight gain is seen in the first month. And it is a serious problem, because patients with schizophrenia, major depression, or bipolar disorder already have an increased risk of premature mortality, especially from cardiovascular diseases, and they have an increased risk of metabolic syndrome. And we sometimes give drugs that further increase that risk,” she said.

Being overweight is a major criterion for defining metabolic syndrome. Dr. Michat noted that, among the antipsychotic drugs that increase weight the most are clozapine, olanzapine, chlorpromazine, quetiapine, and risperidone, in addition to other psychoactive drugs, such as valproic acid, lithium, mirtazapine, and tricyclic antidepressants.

Several clinical trials, such as a pioneering Chinese study from 2008, have shown the potential of metformin to mitigate the weight gain induced by this type of drug.

However, Dr. Michat noted that so far the major guidelines (for example, the Canadian Network for Mood and Anxiety Treatments [CANMAT]/International Society for Bipolar Disorders [ISBD] for bipolar disorder and the American Psychiatric Association [APA] for schizophrenia) “say very little” on how to address this complication. They propose what she defined as a “problematic” order of action in which the initial emphasis is on promoting lifestyle changes, which are difficult for these patients to carry out, as well as general proposals for changing medication (which is not simple to implement when the patient’s condition is stabilized) and eventual consultation with a clinician to start therapy with metformin or other drugs, such as liraglutide, semaglutide, and topiramate.

The new clinical practice guideline, which was published in Evidence-Based Mental Health (of the BMJ journal group), was written by a multidisciplinary team of pharmacists, psychiatrists, and mental health nurses from Ireland. It aims to fill that gap. The investigators reviewed 1,270 scientific articles and analyzed 26 of them in depth, including seven randomized clinical trials and a 2016 systematic review and meta-analysis. The authors made a “strong” recommendation, for which there was moderate-quality evidence, that for patients for whom a lifestyle intervention is unacceptable or inappropriate the use of metformin is an “alternative first-line intervention” for antipsychotic drug–induced weight gain.

Likewise, as a strong recommendation with moderate-quality evidence, the guidance encourages the use of metformin when nonpharmacologic intervention does not seem to be effective.

The guideline also says it is preferable to start metformin early for patients who gain more than 7% of their baseline weight within the first month of antipsychotic treatment. It also endorses metformin when weight gain is established.

Other recommendations include evaluating baseline kidney function before starting metformin treatment and suggest a dose adjustment when the estimated glomerular filtration rate (eGFR) is < 60 mL/min/1.73 m². The guidance says the use of metformin is contraindicated for patients in whom eGFR is <30 mL/min per 1.73 m². The proposed starting dosage is 500 mg twice per day with meals, with increments of 500 mg every 1-2 weeks until reaching a target dose of 2,000 mg/day. The guidance recommends that consideration always be given to individual tolerability and efficacy.

Treatment goals should be personalized and agreed upon with patients. In the case of early intervention, the guideline proposes initially stabilizing the weight gained or, if possible, reverse excess weight. When weight gain is established, the goal would be to lose at least 5% of the weight within the next 6 months.

The authors also recommend monitoring kidney function annually, as well as vitamin B₁₂ levels and individual tolerability and compliance. Gastrointestinal adverse effects can be managed by dose reduction or slower dose titration. The risk of lactic acidosis, which affects 4.3 per 100,000 person-years among those taking metformin, can be attenuated by adjusting the dose according to kidney function or avoiding prescribing it to patients who have a history of alcohol abuse or who are receiving treatment that may interact with the drug.
 

Validating pharmacologic management

The lead author of the new guideline, Ita Fitzgerald, a teacher in clinical pharmacy and senior pharmacist at St. Patrick’s Mental Health Services in Dublin, pointed out that there is a bias toward not using drugs for weight management and shifting the responsibility onto the patients themselves, something that is very often out of their control.

“The purpose of the guideline was to decide on a range of criteria to maximize the use of metformin, to recognize that for many people, pharmacological management is a valid and important option that could and should be more widely used and to provide precise and practical guidance to physicians to facilitate a more widespread use,” Ms. Fitzgerald said in an interview.

According to Fitzgerald, who is pursuing her doctorate at University College Cork (Ireland), one of the most outstanding results of the work is that it highlights that the main benefit of metformin is to flatten rather than reverse antipsychotic-induced weight gain and that indicating it late can nullify that effect.

“In all the recommendations, we try very hard to shift the focus from metformin’s role as a weight reversal agent to one as a weight management agent that should be used early in treatment, which is when most weight gain occurs. If metformin succeeds in flattening that increase, that’s a huge potential benefit for an inexpensive and easily accessible drug. When people have already established weight gain, metformin may not be enough and alternative treatments should be used,” she said.

In addition to its effects on weight, metformin has many other potential health benefits. Of particular importance is that it reduces hyperphagia-mediated antipsychotic-induced weight gain, Ms. Fitzgerald pointed out.

“This is subjectively very important for patients and provides a more positive experience when taking antipsychotics. Antipsychotic-induced weight gain is one of the main reasons for premature discontinuation or incomplete adherence to these drugs and therefore needs to be addressed proactively,” she concluded.

Ms. Fitzgerald and Dr. Michat have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

MAR DEL PLATA, ARGENTINA – Psychiatrists should prescribe metformin early to patients who experience rapid weight gain after they begin taking antipsychotic drugs, according to a new evidence-based Irish guideline for the management of this common complication in adults with psychoses who are taking medications.

The document was discussed during one of the sessions of the XXXV Argentine Congress of Psychiatry of the Association of Argentine Psychiatrists. The document also was presented by one of its authors at the European Congress on Obesity 2022.

The guideline encourages psychiatrists not to underestimate the adverse metabolic effects of their treatments and encourages them to contemplate and carry out this prevention and management strategy, commented María Delia Michat, PhD, professor of clinical psychiatry and psychopharmacology at the APSA Postgraduate Training Institute, Buenos Aires.

“Although it is always good to work as a team, it is usually we psychiatrists who coordinate the pharmacological treatment of our patients, and we have to know how to manage drugs that can prevent cardiovascular disease,” Dr. Michat said in an interview.

“The new guideline is helpful because it protocolizes the use of metformin, which is the cheapest drug and has the most evidence for antipsychotic-induced weight gain,” she added.
 

Avoiding metabolic syndrome

In patients with schizophrenia, obesity rates are 40% higher than in the general population, and 80% of patients develop weight gain after their first treatment, noted Dr. Michat. “Right away, weight gain is seen in the first month. And it is a serious problem, because patients with schizophrenia, major depression, or bipolar disorder already have an increased risk of premature mortality, especially from cardiovascular diseases, and they have an increased risk of metabolic syndrome. And we sometimes give drugs that further increase that risk,” she said.

Being overweight is a major criterion for defining metabolic syndrome. Dr. Michat noted that, among the antipsychotic drugs that increase weight the most are clozapine, olanzapine, chlorpromazine, quetiapine, and risperidone, in addition to other psychoactive drugs, such as valproic acid, lithium, mirtazapine, and tricyclic antidepressants.

Several clinical trials, such as a pioneering Chinese study from 2008, have shown the potential of metformin to mitigate the weight gain induced by this type of drug.

However, Dr. Michat noted that so far the major guidelines (for example, the Canadian Network for Mood and Anxiety Treatments [CANMAT]/International Society for Bipolar Disorders [ISBD] for bipolar disorder and the American Psychiatric Association [APA] for schizophrenia) “say very little” on how to address this complication. They propose what she defined as a “problematic” order of action in which the initial emphasis is on promoting lifestyle changes, which are difficult for these patients to carry out, as well as general proposals for changing medication (which is not simple to implement when the patient’s condition is stabilized) and eventual consultation with a clinician to start therapy with metformin or other drugs, such as liraglutide, semaglutide, and topiramate.

The new clinical practice guideline, which was published in Evidence-Based Mental Health (of the BMJ journal group), was written by a multidisciplinary team of pharmacists, psychiatrists, and mental health nurses from Ireland. It aims to fill that gap. The investigators reviewed 1,270 scientific articles and analyzed 26 of them in depth, including seven randomized clinical trials and a 2016 systematic review and meta-analysis. The authors made a “strong” recommendation, for which there was moderate-quality evidence, that for patients for whom a lifestyle intervention is unacceptable or inappropriate the use of metformin is an “alternative first-line intervention” for antipsychotic drug–induced weight gain.

Likewise, as a strong recommendation with moderate-quality evidence, the guidance encourages the use of metformin when nonpharmacologic intervention does not seem to be effective.

The guideline also says it is preferable to start metformin early for patients who gain more than 7% of their baseline weight within the first month of antipsychotic treatment. It also endorses metformin when weight gain is established.

Other recommendations include evaluating baseline kidney function before starting metformin treatment and suggest a dose adjustment when the estimated glomerular filtration rate (eGFR) is < 60 mL/min/1.73 m². The guidance says the use of metformin is contraindicated for patients in whom eGFR is <30 mL/min per 1.73 m². The proposed starting dosage is 500 mg twice per day with meals, with increments of 500 mg every 1-2 weeks until reaching a target dose of 2,000 mg/day. The guidance recommends that consideration always be given to individual tolerability and efficacy.

Treatment goals should be personalized and agreed upon with patients. In the case of early intervention, the guideline proposes initially stabilizing the weight gained or, if possible, reverse excess weight. When weight gain is established, the goal would be to lose at least 5% of the weight within the next 6 months.

The authors also recommend monitoring kidney function annually, as well as vitamin B₁₂ levels and individual tolerability and compliance. Gastrointestinal adverse effects can be managed by dose reduction or slower dose titration. The risk of lactic acidosis, which affects 4.3 per 100,000 person-years among those taking metformin, can be attenuated by adjusting the dose according to kidney function or avoiding prescribing it to patients who have a history of alcohol abuse or who are receiving treatment that may interact with the drug.
 

Validating pharmacologic management

The lead author of the new guideline, Ita Fitzgerald, a teacher in clinical pharmacy and senior pharmacist at St. Patrick’s Mental Health Services in Dublin, pointed out that there is a bias toward not using drugs for weight management and shifting the responsibility onto the patients themselves, something that is very often out of their control.

“The purpose of the guideline was to decide on a range of criteria to maximize the use of metformin, to recognize that for many people, pharmacological management is a valid and important option that could and should be more widely used and to provide precise and practical guidance to physicians to facilitate a more widespread use,” Ms. Fitzgerald said in an interview.

According to Fitzgerald, who is pursuing her doctorate at University College Cork (Ireland), one of the most outstanding results of the work is that it highlights that the main benefit of metformin is to flatten rather than reverse antipsychotic-induced weight gain and that indicating it late can nullify that effect.

“In all the recommendations, we try very hard to shift the focus from metformin’s role as a weight reversal agent to one as a weight management agent that should be used early in treatment, which is when most weight gain occurs. If metformin succeeds in flattening that increase, that’s a huge potential benefit for an inexpensive and easily accessible drug. When people have already established weight gain, metformin may not be enough and alternative treatments should be used,” she said.

In addition to its effects on weight, metformin has many other potential health benefits. Of particular importance is that it reduces hyperphagia-mediated antipsychotic-induced weight gain, Ms. Fitzgerald pointed out.

“This is subjectively very important for patients and provides a more positive experience when taking antipsychotics. Antipsychotic-induced weight gain is one of the main reasons for premature discontinuation or incomplete adherence to these drugs and therefore needs to be addressed proactively,” she concluded.

Ms. Fitzgerald and Dr. Michat have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

MAR DEL PLATA, ARGENTINA – Psychiatrists should prescribe metformin early to patients who experience rapid weight gain after they begin taking antipsychotic drugs, according to a new evidence-based Irish guideline for the management of this common complication in adults with psychoses who are taking medications.

The document was discussed during one of the sessions of the XXXV Argentine Congress of Psychiatry of the Association of Argentine Psychiatrists. The document also was presented by one of its authors at the European Congress on Obesity 2022.

The guideline encourages psychiatrists not to underestimate the adverse metabolic effects of their treatments and encourages them to contemplate and carry out this prevention and management strategy, commented María Delia Michat, PhD, professor of clinical psychiatry and psychopharmacology at the APSA Postgraduate Training Institute, Buenos Aires.

“Although it is always good to work as a team, it is usually we psychiatrists who coordinate the pharmacological treatment of our patients, and we have to know how to manage drugs that can prevent cardiovascular disease,” Dr. Michat said in an interview.

“The new guideline is helpful because it protocolizes the use of metformin, which is the cheapest drug and has the most evidence for antipsychotic-induced weight gain,” she added.
 

Avoiding metabolic syndrome

In patients with schizophrenia, obesity rates are 40% higher than in the general population, and 80% of patients develop weight gain after their first treatment, noted Dr. Michat. “Right away, weight gain is seen in the first month. And it is a serious problem, because patients with schizophrenia, major depression, or bipolar disorder already have an increased risk of premature mortality, especially from cardiovascular diseases, and they have an increased risk of metabolic syndrome. And we sometimes give drugs that further increase that risk,” she said.

Being overweight is a major criterion for defining metabolic syndrome. Dr. Michat noted that, among the antipsychotic drugs that increase weight the most are clozapine, olanzapine, chlorpromazine, quetiapine, and risperidone, in addition to other psychoactive drugs, such as valproic acid, lithium, mirtazapine, and tricyclic antidepressants.

Several clinical trials, such as a pioneering Chinese study from 2008, have shown the potential of metformin to mitigate the weight gain induced by this type of drug.

However, Dr. Michat noted that so far the major guidelines (for example, the Canadian Network for Mood and Anxiety Treatments [CANMAT]/International Society for Bipolar Disorders [ISBD] for bipolar disorder and the American Psychiatric Association [APA] for schizophrenia) “say very little” on how to address this complication. They propose what she defined as a “problematic” order of action in which the initial emphasis is on promoting lifestyle changes, which are difficult for these patients to carry out, as well as general proposals for changing medication (which is not simple to implement when the patient’s condition is stabilized) and eventual consultation with a clinician to start therapy with metformin or other drugs, such as liraglutide, semaglutide, and topiramate.

The new clinical practice guideline, which was published in Evidence-Based Mental Health (of the BMJ journal group), was written by a multidisciplinary team of pharmacists, psychiatrists, and mental health nurses from Ireland. It aims to fill that gap. The investigators reviewed 1,270 scientific articles and analyzed 26 of them in depth, including seven randomized clinical trials and a 2016 systematic review and meta-analysis. The authors made a “strong” recommendation, for which there was moderate-quality evidence, that for patients for whom a lifestyle intervention is unacceptable or inappropriate the use of metformin is an “alternative first-line intervention” for antipsychotic drug–induced weight gain.

Likewise, as a strong recommendation with moderate-quality evidence, the guidance encourages the use of metformin when nonpharmacologic intervention does not seem to be effective.

The guideline also says it is preferable to start metformin early for patients who gain more than 7% of their baseline weight within the first month of antipsychotic treatment. It also endorses metformin when weight gain is established.

Other recommendations include evaluating baseline kidney function before starting metformin treatment and suggest a dose adjustment when the estimated glomerular filtration rate (eGFR) is < 60 mL/min/1.73 m². The guidance says the use of metformin is contraindicated for patients in whom eGFR is <30 mL/min per 1.73 m². The proposed starting dosage is 500 mg twice per day with meals, with increments of 500 mg every 1-2 weeks until reaching a target dose of 2,000 mg/day. The guidance recommends that consideration always be given to individual tolerability and efficacy.

Treatment goals should be personalized and agreed upon with patients. In the case of early intervention, the guideline proposes initially stabilizing the weight gained or, if possible, reverse excess weight. When weight gain is established, the goal would be to lose at least 5% of the weight within the next 6 months.

The authors also recommend monitoring kidney function annually, as well as vitamin B₁₂ levels and individual tolerability and compliance. Gastrointestinal adverse effects can be managed by dose reduction or slower dose titration. The risk of lactic acidosis, which affects 4.3 per 100,000 person-years among those taking metformin, can be attenuated by adjusting the dose according to kidney function or avoiding prescribing it to patients who have a history of alcohol abuse or who are receiving treatment that may interact with the drug.
 

Validating pharmacologic management

The lead author of the new guideline, Ita Fitzgerald, a teacher in clinical pharmacy and senior pharmacist at St. Patrick’s Mental Health Services in Dublin, pointed out that there is a bias toward not using drugs for weight management and shifting the responsibility onto the patients themselves, something that is very often out of their control.

“The purpose of the guideline was to decide on a range of criteria to maximize the use of metformin, to recognize that for many people, pharmacological management is a valid and important option that could and should be more widely used and to provide precise and practical guidance to physicians to facilitate a more widespread use,” Ms. Fitzgerald said in an interview.

According to Fitzgerald, who is pursuing her doctorate at University College Cork (Ireland), one of the most outstanding results of the work is that it highlights that the main benefit of metformin is to flatten rather than reverse antipsychotic-induced weight gain and that indicating it late can nullify that effect.

“In all the recommendations, we try very hard to shift the focus from metformin’s role as a weight reversal agent to one as a weight management agent that should be used early in treatment, which is when most weight gain occurs. If metformin succeeds in flattening that increase, that’s a huge potential benefit for an inexpensive and easily accessible drug. When people have already established weight gain, metformin may not be enough and alternative treatments should be used,” she said.

In addition to its effects on weight, metformin has many other potential health benefits. Of particular importance is that it reduces hyperphagia-mediated antipsychotic-induced weight gain, Ms. Fitzgerald pointed out.

“This is subjectively very important for patients and provides a more positive experience when taking antipsychotics. Antipsychotic-induced weight gain is one of the main reasons for premature discontinuation or incomplete adherence to these drugs and therefore needs to be addressed proactively,” she concluded.

Ms. Fitzgerald and Dr. Michat have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

A wearable patch that delivers electrical stimulation to the perineum may postpone premature ejaculation, according to research presented at the annual meeting of the American Urological Association. The disposable device appears to work by helping men contract the muscles in the pelvic floor, allowing them to postpone climax.

Among 34 men with a lifelong history of premature ejaculation, average intravaginal ejaculatory latency time – the time from vaginal penetration to ejaculation – increased from about 67 seconds at baseline to 123 seconds when they used the device.

Another 17 participants received a sham treatment – stimulation they could feel but that did not activate muscles. In this group, time to ejaculation increased from 63 seconds to 81 seconds.

The longer duration with active treatment was statistically significant (P < .0001), whereas the increase in the control group was not (P = .1653), said Ege Can Serefoglu, MD, a researcher at Biruni University, Istanbul, and editor-in-chief of the International Journal of Impotence Research.

Dr. Serefoglu is a member of the scientific advisory board for Virility Medical, a company in Hod Hasharon, Israel, that is developing the stimulator. Marketed as vPatch, the device is expected to be available in 2023, Dr. Serefoglu said. It was cleared by the Food and Drug Administration in November and has CE-mark approval in Europe, according to the company.
 

Common problem, limited options

Research shows that 20%-30% of men are not happy with their time to ejaculation, Dr. Serefoglu said.

The International Society for Sexual Medicine defines premature ejaculation as ejaculation which always or almost always occurs within about 1 minute of penetration, the patient is unable to delay this occurrence, and the condition causes personal distress.

“Unfortunately, in spite of its high prevalence we do not really have any satisfying treatment options,” Dr. Serefoglu said.

Topical anesthetics may be used to decrease the sensitivity of the glans penis, and selective serotonin reuptake inhibitors may help delay ejaculation. But these options have limited efficacy and low adherence, he said.

Preclinical studies have shown that injection of botulinum toxin into the bulbospongiosus muscles is associated with a dose-dependent increase in ejaculation latency in rats.

Data on ClinicalTrials.gov show that this approach also may increase ejaculation latency in men, Dr. Serefoglu said. Although investigators found no safety concerns, drugmaker Allergan made a strategic business decision to stop developing this treatment approach, according to the registration entry for the study.

The idea for vPatch came from researchers wondering if instead of paralyzing the muscles with botulinum toxin, they used electrical stimulation to cause contraction of those muscles, Dr. Serefoglu said. A smaller proof-of-concept study demonstrated the feasibility and safety of this technique.

To further assess the safety and efficacy of a transcutaneous perineal electrical stimulator for the treatment of premature ejaculation, investigators conducted the randomized, double-blind, sham-controlled trial at Rambam Medical Centre, Haifa, Israel, and Villa Donatello Clinic, Florence, Italy.

The trial included males with premature ejaculation aged 18-60 years. Their female partners measured IELT using a stopwatch during four sexual intercourse sessions before treatment, and four times on treatment, at home.

In addition to the increased time to ejaculation, perceived control over ejaculation, satisfaction with sexual intercourse, personal distress related to ejaculation, and interpersonal difficulty related to ejaculation all significantly improved with vPatch, the researchers found.

Of participants who received active treatment, 73.5% reported a subjective sense of improvement versus 41.2% of the control group.
 

Potential reactions

No serious adverse events were observed, Dr. Serefoglu reported. Potential adverse reactions include redness, discomfort, and localized pain, according to the company’s website.

Men should not use vPatch if they have been diagnosed with pelvic cancer, or if they have an implanted electronic device, diabetes with peripheral neuropathy, or perineal dermatologic diseases, irritations, or lesions. Other precautions include avoiding use of the vPatch in water or humid environments. The device has not been tested on use with a pregnant partner.

The disposable patches are meant for one-time use. “The miniaturized perineal stimulation device may become an on-demand, drug-free therapeutic option,” Dr. Serefoglu said.

Combining electrical stimulation with other treatment approaches may provide additional benefit, said Bradley Schwartz, DO, professor and chairman of urology at Southern Illinois University, Springfield, who moderated the session at the AUA meeting at which the results of the study were presented.

“You go from 1 to 2 minutes just with this device,” Dr. Schwartz said. “If you went from 2 to 3 minutes, you would essentially be tripling their pleasure or their time, which might make a significant difference.”

Serefoglu agreed that combining the stimulator with other treatment approaches such as topical anesthetics could increase patient satisfaction.

Comoderator Kelly Healy, MD, assistant professor of urology at Columbia University Medical Center, New York, highlighted a direction for future research: examining outcomes according to different types of relationships, as well as partner satisfaction.

“That is a perfect question that should also be considered in the future trials,” Dr. Serefoglu said. “This was mainly focused on the man’s satisfaction. But men are trying to delay their ejaculation to satisfy their partner.”

Dr. Serefoglu is on the scientific advisory board for Virility Medical, which sponsored the study. Dr. Healy had no disclosures. Dr. Schwartz disclosed ties to Cook Medical.

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

A wearable patch that delivers electrical stimulation to the perineum may postpone premature ejaculation, according to research presented at the annual meeting of the American Urological Association. The disposable device appears to work by helping men contract the muscles in the pelvic floor, allowing them to postpone climax.

Among 34 men with a lifelong history of premature ejaculation, average intravaginal ejaculatory latency time – the time from vaginal penetration to ejaculation – increased from about 67 seconds at baseline to 123 seconds when they used the device.

Another 17 participants received a sham treatment – stimulation they could feel but that did not activate muscles. In this group, time to ejaculation increased from 63 seconds to 81 seconds.

The longer duration with active treatment was statistically significant (P < .0001), whereas the increase in the control group was not (P = .1653), said Ege Can Serefoglu, MD, a researcher at Biruni University, Istanbul, and editor-in-chief of the International Journal of Impotence Research.

Dr. Serefoglu is a member of the scientific advisory board for Virility Medical, a company in Hod Hasharon, Israel, that is developing the stimulator. Marketed as vPatch, the device is expected to be available in 2023, Dr. Serefoglu said. It was cleared by the Food and Drug Administration in November and has CE-mark approval in Europe, according to the company.
 

Common problem, limited options

Research shows that 20%-30% of men are not happy with their time to ejaculation, Dr. Serefoglu said.

The International Society for Sexual Medicine defines premature ejaculation as ejaculation which always or almost always occurs within about 1 minute of penetration, the patient is unable to delay this occurrence, and the condition causes personal distress.

“Unfortunately, in spite of its high prevalence we do not really have any satisfying treatment options,” Dr. Serefoglu said.

Topical anesthetics may be used to decrease the sensitivity of the glans penis, and selective serotonin reuptake inhibitors may help delay ejaculation. But these options have limited efficacy and low adherence, he said.

Preclinical studies have shown that injection of botulinum toxin into the bulbospongiosus muscles is associated with a dose-dependent increase in ejaculation latency in rats.

Data on ClinicalTrials.gov show that this approach also may increase ejaculation latency in men, Dr. Serefoglu said. Although investigators found no safety concerns, drugmaker Allergan made a strategic business decision to stop developing this treatment approach, according to the registration entry for the study.

The idea for vPatch came from researchers wondering if instead of paralyzing the muscles with botulinum toxin, they used electrical stimulation to cause contraction of those muscles, Dr. Serefoglu said. A smaller proof-of-concept study demonstrated the feasibility and safety of this technique.

To further assess the safety and efficacy of a transcutaneous perineal electrical stimulator for the treatment of premature ejaculation, investigators conducted the randomized, double-blind, sham-controlled trial at Rambam Medical Centre, Haifa, Israel, and Villa Donatello Clinic, Florence, Italy.

The trial included males with premature ejaculation aged 18-60 years. Their female partners measured IELT using a stopwatch during four sexual intercourse sessions before treatment, and four times on treatment, at home.

In addition to the increased time to ejaculation, perceived control over ejaculation, satisfaction with sexual intercourse, personal distress related to ejaculation, and interpersonal difficulty related to ejaculation all significantly improved with vPatch, the researchers found.

Of participants who received active treatment, 73.5% reported a subjective sense of improvement versus 41.2% of the control group.
 

Potential reactions

No serious adverse events were observed, Dr. Serefoglu reported. Potential adverse reactions include redness, discomfort, and localized pain, according to the company’s website.

Men should not use vPatch if they have been diagnosed with pelvic cancer, or if they have an implanted electronic device, diabetes with peripheral neuropathy, or perineal dermatologic diseases, irritations, or lesions. Other precautions include avoiding use of the vPatch in water or humid environments. The device has not been tested on use with a pregnant partner.

The disposable patches are meant for one-time use. “The miniaturized perineal stimulation device may become an on-demand, drug-free therapeutic option,” Dr. Serefoglu said.

Combining electrical stimulation with other treatment approaches may provide additional benefit, said Bradley Schwartz, DO, professor and chairman of urology at Southern Illinois University, Springfield, who moderated the session at the AUA meeting at which the results of the study were presented.

“You go from 1 to 2 minutes just with this device,” Dr. Schwartz said. “If you went from 2 to 3 minutes, you would essentially be tripling their pleasure or their time, which might make a significant difference.”

Serefoglu agreed that combining the stimulator with other treatment approaches such as topical anesthetics could increase patient satisfaction.

Comoderator Kelly Healy, MD, assistant professor of urology at Columbia University Medical Center, New York, highlighted a direction for future research: examining outcomes according to different types of relationships, as well as partner satisfaction.

“That is a perfect question that should also be considered in the future trials,” Dr. Serefoglu said. “This was mainly focused on the man’s satisfaction. But men are trying to delay their ejaculation to satisfy their partner.”

Dr. Serefoglu is on the scientific advisory board for Virility Medical, which sponsored the study. Dr. Healy had no disclosures. Dr. Schwartz disclosed ties to Cook Medical.

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

A wearable patch that delivers electrical stimulation to the perineum may postpone premature ejaculation, according to research presented at the annual meeting of the American Urological Association. The disposable device appears to work by helping men contract the muscles in the pelvic floor, allowing them to postpone climax.

Among 34 men with a lifelong history of premature ejaculation, average intravaginal ejaculatory latency time – the time from vaginal penetration to ejaculation – increased from about 67 seconds at baseline to 123 seconds when they used the device.

Another 17 participants received a sham treatment – stimulation they could feel but that did not activate muscles. In this group, time to ejaculation increased from 63 seconds to 81 seconds.

The longer duration with active treatment was statistically significant (P < .0001), whereas the increase in the control group was not (P = .1653), said Ege Can Serefoglu, MD, a researcher at Biruni University, Istanbul, and editor-in-chief of the International Journal of Impotence Research.

Dr. Serefoglu is a member of the scientific advisory board for Virility Medical, a company in Hod Hasharon, Israel, that is developing the stimulator. Marketed as vPatch, the device is expected to be available in 2023, Dr. Serefoglu said. It was cleared by the Food and Drug Administration in November and has CE-mark approval in Europe, according to the company.
 

Common problem, limited options

Research shows that 20%-30% of men are not happy with their time to ejaculation, Dr. Serefoglu said.

The International Society for Sexual Medicine defines premature ejaculation as ejaculation which always or almost always occurs within about 1 minute of penetration, the patient is unable to delay this occurrence, and the condition causes personal distress.

“Unfortunately, in spite of its high prevalence we do not really have any satisfying treatment options,” Dr. Serefoglu said.

Topical anesthetics may be used to decrease the sensitivity of the glans penis, and selective serotonin reuptake inhibitors may help delay ejaculation. But these options have limited efficacy and low adherence, he said.

Preclinical studies have shown that injection of botulinum toxin into the bulbospongiosus muscles is associated with a dose-dependent increase in ejaculation latency in rats.

Data on ClinicalTrials.gov show that this approach also may increase ejaculation latency in men, Dr. Serefoglu said. Although investigators found no safety concerns, drugmaker Allergan made a strategic business decision to stop developing this treatment approach, according to the registration entry for the study.

The idea for vPatch came from researchers wondering if instead of paralyzing the muscles with botulinum toxin, they used electrical stimulation to cause contraction of those muscles, Dr. Serefoglu said. A smaller proof-of-concept study demonstrated the feasibility and safety of this technique.

To further assess the safety and efficacy of a transcutaneous perineal electrical stimulator for the treatment of premature ejaculation, investigators conducted the randomized, double-blind, sham-controlled trial at Rambam Medical Centre, Haifa, Israel, and Villa Donatello Clinic, Florence, Italy.

The trial included males with premature ejaculation aged 18-60 years. Their female partners measured IELT using a stopwatch during four sexual intercourse sessions before treatment, and four times on treatment, at home.

In addition to the increased time to ejaculation, perceived control over ejaculation, satisfaction with sexual intercourse, personal distress related to ejaculation, and interpersonal difficulty related to ejaculation all significantly improved with vPatch, the researchers found.

Of participants who received active treatment, 73.5% reported a subjective sense of improvement versus 41.2% of the control group.
 

Potential reactions

No serious adverse events were observed, Dr. Serefoglu reported. Potential adverse reactions include redness, discomfort, and localized pain, according to the company’s website.

Men should not use vPatch if they have been diagnosed with pelvic cancer, or if they have an implanted electronic device, diabetes with peripheral neuropathy, or perineal dermatologic diseases, irritations, or lesions. Other precautions include avoiding use of the vPatch in water or humid environments. The device has not been tested on use with a pregnant partner.

The disposable patches are meant for one-time use. “The miniaturized perineal stimulation device may become an on-demand, drug-free therapeutic option,” Dr. Serefoglu said.

Combining electrical stimulation with other treatment approaches may provide additional benefit, said Bradley Schwartz, DO, professor and chairman of urology at Southern Illinois University, Springfield, who moderated the session at the AUA meeting at which the results of the study were presented.

“You go from 1 to 2 minutes just with this device,” Dr. Schwartz said. “If you went from 2 to 3 minutes, you would essentially be tripling their pleasure or their time, which might make a significant difference.”

Serefoglu agreed that combining the stimulator with other treatment approaches such as topical anesthetics could increase patient satisfaction.

Comoderator Kelly Healy, MD, assistant professor of urology at Columbia University Medical Center, New York, highlighted a direction for future research: examining outcomes according to different types of relationships, as well as partner satisfaction.

“That is a perfect question that should also be considered in the future trials,” Dr. Serefoglu said. “This was mainly focused on the man’s satisfaction. But men are trying to delay their ejaculation to satisfy their partner.”

Dr. Serefoglu is on the scientific advisory board for Virility Medical, which sponsored the study. Dr. Healy had no disclosures. Dr. Schwartz disclosed ties to Cook Medical.

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

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).

Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).

Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).

Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

The Safer Alternatives for Emergency Response (SAFER) program provides a safe supply of substances to prevent drug overdose deaths, according to a new report.

The program has been operating in Vancouver, British Columbia, since April 2021. So far, the program has enrolled 58 participants who have reported benefits from having new options when other forms of treatment or harm reduction didn’t work. In addition, doctors who work with the program have reported increased medication adherence among the participants, as well as better chronic disease management.

Similar safe supply programs are being implemented or considered in other places across Canada. Since 2019, Health Canada has funded 18 safe supply pilot programs.

“When we look at the number of overdose deaths, it should be zero. These are preventable deaths,” author Christy Sutherland, MD, medical director at the PHS Community Services Society, Vancouver, which operates the SAFER program, told this news organization.

PHS Community Services Society

Safe supply programs

Between January 2016 and June 2021, more than 24,000 people died from opioid toxicity in Canada, according to the authors. A key driver of the ongoing public health crisis has been the introduction of illicit fentanyl and other dangerous substances into the unregulated drug supply.

In recent years, several harm-reduction options and substance use disorder treatment programs have been introduced in Canada to stem overdose deaths. However, they haven’t been sufficient, and the number of deaths continues to rise.

“In 2010, methadone worked, but now even high doses don’t keep people out of withdrawal due to the infiltration of fentanyl,” Dr. Sutherland said. “It’s clinically not working anymore. People are now going through benzodiazepine withdrawal and opiate withdrawal at the same time.”

The changes have led doctors to call for programs that provide legal and regulated sources of psychoactive substances, also known as “safe supply” programs. In particular, low-barrier and flexible options are necessary to meet the needs of various people in the community.

In Vancouver, the SAFER program provides medications that are prescribed off-label as substitutes to the illicit drug supply. A multidisciplinary team oversees the program, including doctors, nurses, pharmacists, social workers, and people who have experience living with substance use.

The program’s approach is akin to the use of medications as treatments for substance use disorder, such as opioid-agonist therapy. However, instead of promoting abstinence, the goal of SAFER is to prevent overdose deaths and other consequences by decreasing reliance on the unregulated drug market.

Enrolled participants can access medications, including opioids such as hydromorphone and fentanyl, as a substitute for the unregulated substances that they consume. A notable aspect of SAFER is the offer of fentanyl – with a known potency and without dangerous adulterants found in the local drug supply.
 

Promoting participant autonomy

Given the increasing rate of overdose deaths involving stimulants in Canada, the program also offers prescribed psychostimulants, such as methylphenidate and dextroamphetamine.

The program focuses on harm reduction and promoting participant autonomy. SAFER doesn’t have a predetermined schedule for medication access, which allows participants to return as they need.

“Creating this program has required patience to change our practices,” Dr. Sutherland said. “As you learn more and do more, you’re always growing because you care about your patients and want to help them, especially vulnerable people with a high risk for death.”

The SAFER program is integrated into health care and social services, and participants have access to on-site primary care from clinicians trained in addiction medicine. The program is located alongside a low-barrier prevention site, where supplies such as syringes, take-home naloxone kits, and drug-checking services are available.

The SAFER program will undergo a scientific evaluation, led by two of the co-authors, which will include about 200 participants. During a 2-year period, the evaluation will assess whether the program reduces the risk for overdose deaths and supports access to primary care, harm reduction, and substance use disorder treatment. In addition, the researchers will analyze other key outcomes, such as fatal versus nonfatal overdoses, medication adherence, and the qualitative lived experience of participants.
 

The end of prohibition?

“We’ve had the same challenges with people buying illegal drugs on the street for almost 30 years, but about 5 years ago, that all changed when fentanyl became a prominent drug, and overdose deaths skyrocketed,” Mark Tyndall, MD, a public health professor at the University of British Columbia, Vancouver, said in an interview.

University of British Columbia

Dr. Tyndall is also executive director of the British Columbia Centre for Disease Control and executive director of MySafe Society, a safe supply program in Canada for those with opioid addiction. He is not involved in the SAFER program.

SAFER and MySafe Society are positioned as low-barrier programs, he said, meaning that the public health response is primarily focused on preventing deaths and helping people to get access to medication that won’t kill them. The idea is to meet people where they are today.

However, these programs still face major barriers, such as limitations from federal regulators and stigmas around illicit drugs and harm-reduction programs.

“These beliefs are entrenched, and it takes a long time to help people understand that prohibition means that dangerous drugs are on the street,” he said. “I don’t think way more people are using than 10 years ago, but there was a supply of heroin that was stable in potency back then, and people weren’t dying.”

Ultimately, Dr. Tyndall said, drug policy experts would like to create a regulated supply, similar to the supply of cannabis. The political and regulatory process may take much longer to catch up, but he believes that it’s the most ethical way to reduce overdose deaths and the unregulated drug supply.

“The harshest critics of harm reduction often go to the liquor store every weekend,” he said. “It’s going to be a long process before people think this way, but having fentanyl and other dangerous drugs on the street has signaled the end stage of prohibition.”

The SAFER program is operated by PHS Community Services Society in partnership with Vancouver Coastal Health and funded through Health Canada’s Substance Use and Addiction Program. Dr. Tyndall reported no relevant disclosures.

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

The Safer Alternatives for Emergency Response (SAFER) program provides a safe supply of substances to prevent drug overdose deaths, according to a new report.

The program has been operating in Vancouver, British Columbia, since April 2021. So far, the program has enrolled 58 participants who have reported benefits from having new options when other forms of treatment or harm reduction didn’t work. In addition, doctors who work with the program have reported increased medication adherence among the participants, as well as better chronic disease management.

Similar safe supply programs are being implemented or considered in other places across Canada. Since 2019, Health Canada has funded 18 safe supply pilot programs.

“When we look at the number of overdose deaths, it should be zero. These are preventable deaths,” author Christy Sutherland, MD, medical director at the PHS Community Services Society, Vancouver, which operates the SAFER program, told this news organization.

PHS Community Services Society

Safe supply programs

Between January 2016 and June 2021, more than 24,000 people died from opioid toxicity in Canada, according to the authors. A key driver of the ongoing public health crisis has been the introduction of illicit fentanyl and other dangerous substances into the unregulated drug supply.

In recent years, several harm-reduction options and substance use disorder treatment programs have been introduced in Canada to stem overdose deaths. However, they haven’t been sufficient, and the number of deaths continues to rise.

“In 2010, methadone worked, but now even high doses don’t keep people out of withdrawal due to the infiltration of fentanyl,” Dr. Sutherland said. “It’s clinically not working anymore. People are now going through benzodiazepine withdrawal and opiate withdrawal at the same time.”

The changes have led doctors to call for programs that provide legal and regulated sources of psychoactive substances, also known as “safe supply” programs. In particular, low-barrier and flexible options are necessary to meet the needs of various people in the community.

In Vancouver, the SAFER program provides medications that are prescribed off-label as substitutes to the illicit drug supply. A multidisciplinary team oversees the program, including doctors, nurses, pharmacists, social workers, and people who have experience living with substance use.

The program’s approach is akin to the use of medications as treatments for substance use disorder, such as opioid-agonist therapy. However, instead of promoting abstinence, the goal of SAFER is to prevent overdose deaths and other consequences by decreasing reliance on the unregulated drug market.

Enrolled participants can access medications, including opioids such as hydromorphone and fentanyl, as a substitute for the unregulated substances that they consume. A notable aspect of SAFER is the offer of fentanyl – with a known potency and without dangerous adulterants found in the local drug supply.
 

Promoting participant autonomy

Given the increasing rate of overdose deaths involving stimulants in Canada, the program also offers prescribed psychostimulants, such as methylphenidate and dextroamphetamine.

The program focuses on harm reduction and promoting participant autonomy. SAFER doesn’t have a predetermined schedule for medication access, which allows participants to return as they need.

“Creating this program has required patience to change our practices,” Dr. Sutherland said. “As you learn more and do more, you’re always growing because you care about your patients and want to help them, especially vulnerable people with a high risk for death.”

The SAFER program is integrated into health care and social services, and participants have access to on-site primary care from clinicians trained in addiction medicine. The program is located alongside a low-barrier prevention site, where supplies such as syringes, take-home naloxone kits, and drug-checking services are available.

The SAFER program will undergo a scientific evaluation, led by two of the co-authors, which will include about 200 participants. During a 2-year period, the evaluation will assess whether the program reduces the risk for overdose deaths and supports access to primary care, harm reduction, and substance use disorder treatment. In addition, the researchers will analyze other key outcomes, such as fatal versus nonfatal overdoses, medication adherence, and the qualitative lived experience of participants.
 

The end of prohibition?

“We’ve had the same challenges with people buying illegal drugs on the street for almost 30 years, but about 5 years ago, that all changed when fentanyl became a prominent drug, and overdose deaths skyrocketed,” Mark Tyndall, MD, a public health professor at the University of British Columbia, Vancouver, said in an interview.

University of British Columbia

Dr. Tyndall is also executive director of the British Columbia Centre for Disease Control and executive director of MySafe Society, a safe supply program in Canada for those with opioid addiction. He is not involved in the SAFER program.

SAFER and MySafe Society are positioned as low-barrier programs, he said, meaning that the public health response is primarily focused on preventing deaths and helping people to get access to medication that won’t kill them. The idea is to meet people where they are today.

However, these programs still face major barriers, such as limitations from federal regulators and stigmas around illicit drugs and harm-reduction programs.

“These beliefs are entrenched, and it takes a long time to help people understand that prohibition means that dangerous drugs are on the street,” he said. “I don’t think way more people are using than 10 years ago, but there was a supply of heroin that was stable in potency back then, and people weren’t dying.”

Ultimately, Dr. Tyndall said, drug policy experts would like to create a regulated supply, similar to the supply of cannabis. The political and regulatory process may take much longer to catch up, but he believes that it’s the most ethical way to reduce overdose deaths and the unregulated drug supply.

“The harshest critics of harm reduction often go to the liquor store every weekend,” he said. “It’s going to be a long process before people think this way, but having fentanyl and other dangerous drugs on the street has signaled the end stage of prohibition.”

The SAFER program is operated by PHS Community Services Society in partnership with Vancouver Coastal Health and funded through Health Canada’s Substance Use and Addiction Program. Dr. Tyndall reported no relevant disclosures.

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

The Safer Alternatives for Emergency Response (SAFER) program provides a safe supply of substances to prevent drug overdose deaths, according to a new report.

The program has been operating in Vancouver, British Columbia, since April 2021. So far, the program has enrolled 58 participants who have reported benefits from having new options when other forms of treatment or harm reduction didn’t work. In addition, doctors who work with the program have reported increased medication adherence among the participants, as well as better chronic disease management.

Similar safe supply programs are being implemented or considered in other places across Canada. Since 2019, Health Canada has funded 18 safe supply pilot programs.

“When we look at the number of overdose deaths, it should be zero. These are preventable deaths,” author Christy Sutherland, MD, medical director at the PHS Community Services Society, Vancouver, which operates the SAFER program, told this news organization.

PHS Community Services Society

Safe supply programs

Between January 2016 and June 2021, more than 24,000 people died from opioid toxicity in Canada, according to the authors. A key driver of the ongoing public health crisis has been the introduction of illicit fentanyl and other dangerous substances into the unregulated drug supply.

In recent years, several harm-reduction options and substance use disorder treatment programs have been introduced in Canada to stem overdose deaths. However, they haven’t been sufficient, and the number of deaths continues to rise.

“In 2010, methadone worked, but now even high doses don’t keep people out of withdrawal due to the infiltration of fentanyl,” Dr. Sutherland said. “It’s clinically not working anymore. People are now going through benzodiazepine withdrawal and opiate withdrawal at the same time.”

The changes have led doctors to call for programs that provide legal and regulated sources of psychoactive substances, also known as “safe supply” programs. In particular, low-barrier and flexible options are necessary to meet the needs of various people in the community.

In Vancouver, the SAFER program provides medications that are prescribed off-label as substitutes to the illicit drug supply. A multidisciplinary team oversees the program, including doctors, nurses, pharmacists, social workers, and people who have experience living with substance use.

The program’s approach is akin to the use of medications as treatments for substance use disorder, such as opioid-agonist therapy. However, instead of promoting abstinence, the goal of SAFER is to prevent overdose deaths and other consequences by decreasing reliance on the unregulated drug market.

Enrolled participants can access medications, including opioids such as hydromorphone and fentanyl, as a substitute for the unregulated substances that they consume. A notable aspect of SAFER is the offer of fentanyl – with a known potency and without dangerous adulterants found in the local drug supply.
 

Promoting participant autonomy

Given the increasing rate of overdose deaths involving stimulants in Canada, the program also offers prescribed psychostimulants, such as methylphenidate and dextroamphetamine.

The program focuses on harm reduction and promoting participant autonomy. SAFER doesn’t have a predetermined schedule for medication access, which allows participants to return as they need.

“Creating this program has required patience to change our practices,” Dr. Sutherland said. “As you learn more and do more, you’re always growing because you care about your patients and want to help them, especially vulnerable people with a high risk for death.”

The SAFER program is integrated into health care and social services, and participants have access to on-site primary care from clinicians trained in addiction medicine. The program is located alongside a low-barrier prevention site, where supplies such as syringes, take-home naloxone kits, and drug-checking services are available.

The SAFER program will undergo a scientific evaluation, led by two of the co-authors, which will include about 200 participants. During a 2-year period, the evaluation will assess whether the program reduces the risk for overdose deaths and supports access to primary care, harm reduction, and substance use disorder treatment. In addition, the researchers will analyze other key outcomes, such as fatal versus nonfatal overdoses, medication adherence, and the qualitative lived experience of participants.
 

The end of prohibition?

“We’ve had the same challenges with people buying illegal drugs on the street for almost 30 years, but about 5 years ago, that all changed when fentanyl became a prominent drug, and overdose deaths skyrocketed,” Mark Tyndall, MD, a public health professor at the University of British Columbia, Vancouver, said in an interview.

University of British Columbia

Dr. Tyndall is also executive director of the British Columbia Centre for Disease Control and executive director of MySafe Society, a safe supply program in Canada for those with opioid addiction. He is not involved in the SAFER program.

SAFER and MySafe Society are positioned as low-barrier programs, he said, meaning that the public health response is primarily focused on preventing deaths and helping people to get access to medication that won’t kill them. The idea is to meet people where they are today.

However, these programs still face major barriers, such as limitations from federal regulators and stigmas around illicit drugs and harm-reduction programs.

“These beliefs are entrenched, and it takes a long time to help people understand that prohibition means that dangerous drugs are on the street,” he said. “I don’t think way more people are using than 10 years ago, but there was a supply of heroin that was stable in potency back then, and people weren’t dying.”

Ultimately, Dr. Tyndall said, drug policy experts would like to create a regulated supply, similar to the supply of cannabis. The political and regulatory process may take much longer to catch up, but he believes that it’s the most ethical way to reduce overdose deaths and the unregulated drug supply.

“The harshest critics of harm reduction often go to the liquor store every weekend,” he said. “It’s going to be a long process before people think this way, but having fentanyl and other dangerous drugs on the street has signaled the end stage of prohibition.”

The SAFER program is operated by PHS Community Services Society in partnership with Vancouver Coastal Health and funded through Health Canada’s Substance Use and Addiction Program. Dr. Tyndall reported no relevant disclosures.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Yet another study has found that vitamin D supplementation doesn’t reduce the risk of developing type 2 diabetes in the general population with prediabetes, but it does leave the door open for benefit in those with low insulin secretion.

The new findings come from the prospective Diabetes Prevention With Active Vitamin D (DPVD) trial of more than 1,200 Japanese participants with impaired glucose tolerance.

The data were published online in The BMJ by Tetsuya Kawahara, MD, PhD, of Shin Komonji Hospital, Kitakyushu, Japan, and colleagues.

Treatment with 0.75 μg/day of eldecalcitol, an active vitamin D analogue, for 3 years did not prevent progression from prediabetes to type 2 diabetes, nor did it improve the rate of regression to normoglycemia, compared with placebo.

However, “we showed a preventive effect of eldecalcitol after adjusting for covariables ... The preventive effect of eldecalcitol on development of type 2 diabetes in a prediabetic population was seen especially among participants with insulin insufficiency,” wrote Dr. Kawahara and colleagues.
 

‘Remarkably similar’ results in several trials

The new trial is “well conducted, with rigorously defined and tested diagnostic criteria, and of sufficient duration, but it may have been underpowered to detect a small effect,” Tatiana Christides, MD, PhD, of Queen Mary University of London, wrote in an accompanying editorial.

Dr. Christides notes that a recent meta-analysis of intervention trials did find a significant 10% reduction in risk of type 2 diabetes with vitamin D supplementation, “a difference too small to be detected by the new trial ... Although a 10% risk reduction is modest, it may be valuable at the population level and justifies further study.”

The new finding, a nonsignificant 13% relative reduction in risk, is similar to the 13% relative risk reduction found in the Vitamin D and Type 2 Diabetes (D2d) trial reported in 2019.

But in that study as in this one, there was a suggested benefit in a subset of people. In D2d, it was in those who were vitamin D deficient.  

Asked to comment, D2d lead investigator Anastassios G. Pittas, MD, chief of the division of diabetes, endocrinology, and metabolism at Tufts University, Boston, pointed out that the results were also “remarkably similar” to those of a third study from Norway published in 2014, which also found a 13% relative risk reduction.

“The nearly identical results from the three trials that were specifically designed and conducted to test whether vitamin D supplementation lowers diabetes clearly points to a beneficial effect of vitamin D for diabetes risk reduction. However, the overall effect in people not selected for vitamin D insufficiency seems to be less than hypothesized in each trial,” Dr. Pittas said in an interview.  

He added, “there will be no more specific vitamin D and diabetes prevention trials, so we need to continue gaining insights from these three trials.”

Some patients with prediabetes may benefit from vitamin D

Dr. Pittas advised that although the overall effect is modest in people with prediabetes who aren’t selected for vitamin D deficiency, “given how prevalent prediabetes and type 2 diabetes are, clinicians and patients should consider vitamin D supplementation as an adjunct to weight loss for diabetes prevention. Based on analyses from the D2d study, people with prediabetes who have low levels of vitamin D and are nonobese derive the most benefit.”

He noted that secondary analyses from D2d also suggest greater benefit among those achieving higher blood levels of vitamin D, but that high supplemental doses could cause adverse musculoskeletal outcomes in older adults, “so the benefit–harm ratio needs to be ascertained individually.”

Dr. Christides advised, “Until further data are available from high-quality randomized trials, health care professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”
 

DPVD: Hint of benefit in those with greater insulin resistance

The double-blind, multicenter, randomized, placebo-controlled DPVD trial took place from June 1, 2013, through Aug. 31, 2015, and involved 1,256 participants with impaired glucose tolerance (with or without impaired fasting glucose) from 32 institutions in Japan. They were randomized 1:1 to receive eldecalcitol or placebo for 3 years.

During the 3-year period, 12.5% of the 630 patients in the eldecalcitol group and 14.2% of the 626 patients in the placebo group developed diabetes. The difference was not significant, with a hazard ratio (HR) of 0.87 (P = .39). There was no difference in regression to normoglycemia, which had occurred in 23.0% with eldecalcitol versus 20.1% with placebo by the end of the study (P = .21).

However, eldecalcitol was effective for preventing the development of type 2 diabetes after adjustment for prespecified variables, including age, sex, hypertension, body mass index, family history of diabetes, 2-hour plasma glucose, 25-hydroxyvitamin D, and insulin resistance (HR, 0.69; P = .02).

In a post hoc analysis, eldecalcitol significantly prevented the development of type 2 diabetes among those with the lowest divisions of homeostatic model assessment (HOMA)-β (HR, 0.35; P < .001), HOMA-insulin resistance (HR, 0.37; P = .001), and fasting immunoreactive insulin (HR, 0.41; P = .001).

“These results indicate that eldecalcitol had a beneficial effect on insufficient basal insulin secretion,” Dr. Kawahara and colleagues wrote.

Discontinuations due to adverse events occurred in 4.1% with eldecalcitol and 3.4% in the placebo group (HR, 1.23; P = .47). Rates and types of adverse events didn’t differ significantly between the two groups.

The study was supported by a grant from the Kitakyushu Medical Association. The authors had no further disclosures. Dr. Christides had no disclosures. Dr. Pittas has reported receiving funding from the National Institutes of Health.

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

Yet another study has found that vitamin D supplementation doesn’t reduce the risk of developing type 2 diabetes in the general population with prediabetes, but it does leave the door open for benefit in those with low insulin secretion.

The new findings come from the prospective Diabetes Prevention With Active Vitamin D (DPVD) trial of more than 1,200 Japanese participants with impaired glucose tolerance.

The data were published online in The BMJ by Tetsuya Kawahara, MD, PhD, of Shin Komonji Hospital, Kitakyushu, Japan, and colleagues.

Treatment with 0.75 μg/day of eldecalcitol, an active vitamin D analogue, for 3 years did not prevent progression from prediabetes to type 2 diabetes, nor did it improve the rate of regression to normoglycemia, compared with placebo.

However, “we showed a preventive effect of eldecalcitol after adjusting for covariables ... The preventive effect of eldecalcitol on development of type 2 diabetes in a prediabetic population was seen especially among participants with insulin insufficiency,” wrote Dr. Kawahara and colleagues.
 

‘Remarkably similar’ results in several trials

The new trial is “well conducted, with rigorously defined and tested diagnostic criteria, and of sufficient duration, but it may have been underpowered to detect a small effect,” Tatiana Christides, MD, PhD, of Queen Mary University of London, wrote in an accompanying editorial.

Dr. Christides notes that a recent meta-analysis of intervention trials did find a significant 10% reduction in risk of type 2 diabetes with vitamin D supplementation, “a difference too small to be detected by the new trial ... Although a 10% risk reduction is modest, it may be valuable at the population level and justifies further study.”

The new finding, a nonsignificant 13% relative reduction in risk, is similar to the 13% relative risk reduction found in the Vitamin D and Type 2 Diabetes (D2d) trial reported in 2019.

But in that study as in this one, there was a suggested benefit in a subset of people. In D2d, it was in those who were vitamin D deficient.  

Asked to comment, D2d lead investigator Anastassios G. Pittas, MD, chief of the division of diabetes, endocrinology, and metabolism at Tufts University, Boston, pointed out that the results were also “remarkably similar” to those of a third study from Norway published in 2014, which also found a 13% relative risk reduction.

“The nearly identical results from the three trials that were specifically designed and conducted to test whether vitamin D supplementation lowers diabetes clearly points to a beneficial effect of vitamin D for diabetes risk reduction. However, the overall effect in people not selected for vitamin D insufficiency seems to be less than hypothesized in each trial,” Dr. Pittas said in an interview.  

He added, “there will be no more specific vitamin D and diabetes prevention trials, so we need to continue gaining insights from these three trials.”

Some patients with prediabetes may benefit from vitamin D

Dr. Pittas advised that although the overall effect is modest in people with prediabetes who aren’t selected for vitamin D deficiency, “given how prevalent prediabetes and type 2 diabetes are, clinicians and patients should consider vitamin D supplementation as an adjunct to weight loss for diabetes prevention. Based on analyses from the D2d study, people with prediabetes who have low levels of vitamin D and are nonobese derive the most benefit.”

He noted that secondary analyses from D2d also suggest greater benefit among those achieving higher blood levels of vitamin D, but that high supplemental doses could cause adverse musculoskeletal outcomes in older adults, “so the benefit–harm ratio needs to be ascertained individually.”

Dr. Christides advised, “Until further data are available from high-quality randomized trials, health care professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”
 

DPVD: Hint of benefit in those with greater insulin resistance

The double-blind, multicenter, randomized, placebo-controlled DPVD trial took place from June 1, 2013, through Aug. 31, 2015, and involved 1,256 participants with impaired glucose tolerance (with or without impaired fasting glucose) from 32 institutions in Japan. They were randomized 1:1 to receive eldecalcitol or placebo for 3 years.

During the 3-year period, 12.5% of the 630 patients in the eldecalcitol group and 14.2% of the 626 patients in the placebo group developed diabetes. The difference was not significant, with a hazard ratio (HR) of 0.87 (P = .39). There was no difference in regression to normoglycemia, which had occurred in 23.0% with eldecalcitol versus 20.1% with placebo by the end of the study (P = .21).

However, eldecalcitol was effective for preventing the development of type 2 diabetes after adjustment for prespecified variables, including age, sex, hypertension, body mass index, family history of diabetes, 2-hour plasma glucose, 25-hydroxyvitamin D, and insulin resistance (HR, 0.69; P = .02).

In a post hoc analysis, eldecalcitol significantly prevented the development of type 2 diabetes among those with the lowest divisions of homeostatic model assessment (HOMA)-β (HR, 0.35; P < .001), HOMA-insulin resistance (HR, 0.37; P = .001), and fasting immunoreactive insulin (HR, 0.41; P = .001).

“These results indicate that eldecalcitol had a beneficial effect on insufficient basal insulin secretion,” Dr. Kawahara and colleagues wrote.

Discontinuations due to adverse events occurred in 4.1% with eldecalcitol and 3.4% in the placebo group (HR, 1.23; P = .47). Rates and types of adverse events didn’t differ significantly between the two groups.

The study was supported by a grant from the Kitakyushu Medical Association. The authors had no further disclosures. Dr. Christides had no disclosures. Dr. Pittas has reported receiving funding from the National Institutes of Health.

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

Yet another study has found that vitamin D supplementation doesn’t reduce the risk of developing type 2 diabetes in the general population with prediabetes, but it does leave the door open for benefit in those with low insulin secretion.

The new findings come from the prospective Diabetes Prevention With Active Vitamin D (DPVD) trial of more than 1,200 Japanese participants with impaired glucose tolerance.

The data were published online in The BMJ by Tetsuya Kawahara, MD, PhD, of Shin Komonji Hospital, Kitakyushu, Japan, and colleagues.

Treatment with 0.75 μg/day of eldecalcitol, an active vitamin D analogue, for 3 years did not prevent progression from prediabetes to type 2 diabetes, nor did it improve the rate of regression to normoglycemia, compared with placebo.

However, “we showed a preventive effect of eldecalcitol after adjusting for covariables ... The preventive effect of eldecalcitol on development of type 2 diabetes in a prediabetic population was seen especially among participants with insulin insufficiency,” wrote Dr. Kawahara and colleagues.
 

‘Remarkably similar’ results in several trials

The new trial is “well conducted, with rigorously defined and tested diagnostic criteria, and of sufficient duration, but it may have been underpowered to detect a small effect,” Tatiana Christides, MD, PhD, of Queen Mary University of London, wrote in an accompanying editorial.

Dr. Christides notes that a recent meta-analysis of intervention trials did find a significant 10% reduction in risk of type 2 diabetes with vitamin D supplementation, “a difference too small to be detected by the new trial ... Although a 10% risk reduction is modest, it may be valuable at the population level and justifies further study.”

The new finding, a nonsignificant 13% relative reduction in risk, is similar to the 13% relative risk reduction found in the Vitamin D and Type 2 Diabetes (D2d) trial reported in 2019.

But in that study as in this one, there was a suggested benefit in a subset of people. In D2d, it was in those who were vitamin D deficient.  

Asked to comment, D2d lead investigator Anastassios G. Pittas, MD, chief of the division of diabetes, endocrinology, and metabolism at Tufts University, Boston, pointed out that the results were also “remarkably similar” to those of a third study from Norway published in 2014, which also found a 13% relative risk reduction.

“The nearly identical results from the three trials that were specifically designed and conducted to test whether vitamin D supplementation lowers diabetes clearly points to a beneficial effect of vitamin D for diabetes risk reduction. However, the overall effect in people not selected for vitamin D insufficiency seems to be less than hypothesized in each trial,” Dr. Pittas said in an interview.  

He added, “there will be no more specific vitamin D and diabetes prevention trials, so we need to continue gaining insights from these three trials.”

Some patients with prediabetes may benefit from vitamin D

Dr. Pittas advised that although the overall effect is modest in people with prediabetes who aren’t selected for vitamin D deficiency, “given how prevalent prediabetes and type 2 diabetes are, clinicians and patients should consider vitamin D supplementation as an adjunct to weight loss for diabetes prevention. Based on analyses from the D2d study, people with prediabetes who have low levels of vitamin D and are nonobese derive the most benefit.”

He noted that secondary analyses from D2d also suggest greater benefit among those achieving higher blood levels of vitamin D, but that high supplemental doses could cause adverse musculoskeletal outcomes in older adults, “so the benefit–harm ratio needs to be ascertained individually.”

Dr. Christides advised, “Until further data are available from high-quality randomized trials, health care professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”
 

DPVD: Hint of benefit in those with greater insulin resistance

The double-blind, multicenter, randomized, placebo-controlled DPVD trial took place from June 1, 2013, through Aug. 31, 2015, and involved 1,256 participants with impaired glucose tolerance (with or without impaired fasting glucose) from 32 institutions in Japan. They were randomized 1:1 to receive eldecalcitol or placebo for 3 years.

During the 3-year period, 12.5% of the 630 patients in the eldecalcitol group and 14.2% of the 626 patients in the placebo group developed diabetes. The difference was not significant, with a hazard ratio (HR) of 0.87 (P = .39). There was no difference in regression to normoglycemia, which had occurred in 23.0% with eldecalcitol versus 20.1% with placebo by the end of the study (P = .21).

However, eldecalcitol was effective for preventing the development of type 2 diabetes after adjustment for prespecified variables, including age, sex, hypertension, body mass index, family history of diabetes, 2-hour plasma glucose, 25-hydroxyvitamin D, and insulin resistance (HR, 0.69; P = .02).

In a post hoc analysis, eldecalcitol significantly prevented the development of type 2 diabetes among those with the lowest divisions of homeostatic model assessment (HOMA)-β (HR, 0.35; P < .001), HOMA-insulin resistance (HR, 0.37; P = .001), and fasting immunoreactive insulin (HR, 0.41; P = .001).

“These results indicate that eldecalcitol had a beneficial effect on insufficient basal insulin secretion,” Dr. Kawahara and colleagues wrote.

Discontinuations due to adverse events occurred in 4.1% with eldecalcitol and 3.4% in the placebo group (HR, 1.23; P = .47). Rates and types of adverse events didn’t differ significantly between the two groups.

The study was supported by a grant from the Kitakyushu Medical Association. The authors had no further disclosures. Dr. Christides had no disclosures. Dr. Pittas has reported receiving funding from the National Institutes of Health.

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