Diabetes

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

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

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

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

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

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

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of bupropion/naltrexone to glucagon-like peptide 1 (GLP-1) receptor agonists leads to a further 4%-5% total body weight loss (TBWL) in patients with obesity, including those who show a poor response to initial GLP-1 monotherapy.

METHODOLOGY:

• Some patients with obesity experience suboptimal weight loss with GLP-1 monotherapy; however, adding treatments targeting multiple pathways may offer synergistic effects and improve outcomes.
• Researchers retrospectively evaluated adult patients with body mass index (BMI) ≥ 30 who attended an obesity clinic in Vancouver, Canada, and received a GLP-1 receptor agonist (liraglutide or semaglutide) for at least 6 months.
• They compared patients who continued receiving GLP-1 monotherapy with those who received add-on bupropion/naltrexone (combination therapy).
• The percent TBWL was compared between the groups from the initiation of the GLP-1 or the addition of bupropion/naltrexone over a period of 6 and 12 months.
• Patients prescribed combination therapy were stratified into responders (≥ 5% TBWL) and nonresponders (< 5% TBWL) based on their initial response to GLP-1 monotherapy.

TAKEAWAY:

• Researchers included 415 patients with BMI ≥ 30 (mean age, 47.3 years; 75.6% women), of whom 320 continued receiving GLP-1 monotherapy and 95 received add-on bupropion/naltrexone (combination therapy); the mean follow-up period was 510.9 days.
• At 12 months, there was no significant difference in the percent TBWL among patients receiving the GLP-1 monotherapy or combination therapy (9.6% TBWL in both).
• However, when patients were stratified by their initial GLP-1 response, combination therapy led to a greater percent TBWL than monotherapy in both responders (P = .002) and nonresponders (P < .0001).
• After the addition of bupropion/naltrexone, the mean percent TBWL was 4.3% (P < .001) and 5.3% (P = .009) at 6 and 12 months, respectively, among the responders, and 3.7% (P = .009) and 4.0% (P = .02) at 6 and 12 months, respectively, among the nonresponders.

IN PRACTICE:

“Specific characteristics of individuals who benefit from the bupropion/naltrexone augmentation should be examined to identify patient populations wherein this may be of greatest benefit,” the authors wrote.

SOURCE:

This study, led by James Naude, Faculty of Medicine, University of British Columbia, Vancouver, Canada, was published in the International Journal of Obesity.

LIMITATIONS:

Virtual care and self-reported weights by patients owing to the COVID-19 pandemic could have introduced bias. Some of the data on weight and medication adherence were missing. Moreover, there was no placebo control; hence, there may be confounding by indication.

DISCLOSURES:

The study was not supported by any specific funding. Two of the authors reported receiving educational grants and speaker fees, with one currently being an advisory board member to various pharma companies and the other an advisory board member to a pharma company in the past.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of bupropion/naltrexone to glucagon-like peptide 1 (GLP-1) receptor agonists leads to a further 4%-5% total body weight loss (TBWL) in patients with obesity, including those who show a poor response to initial GLP-1 monotherapy.

METHODOLOGY:

• Some patients with obesity experience suboptimal weight loss with GLP-1 monotherapy; however, adding treatments targeting multiple pathways may offer synergistic effects and improve outcomes.
• Researchers retrospectively evaluated adult patients with body mass index (BMI) ≥ 30 who attended an obesity clinic in Vancouver, Canada, and received a GLP-1 receptor agonist (liraglutide or semaglutide) for at least 6 months.
• They compared patients who continued receiving GLP-1 monotherapy with those who received add-on bupropion/naltrexone (combination therapy).
• The percent TBWL was compared between the groups from the initiation of the GLP-1 or the addition of bupropion/naltrexone over a period of 6 and 12 months.
• Patients prescribed combination therapy were stratified into responders (≥ 5% TBWL) and nonresponders (< 5% TBWL) based on their initial response to GLP-1 monotherapy.

TAKEAWAY:

• Researchers included 415 patients with BMI ≥ 30 (mean age, 47.3 years; 75.6% women), of whom 320 continued receiving GLP-1 monotherapy and 95 received add-on bupropion/naltrexone (combination therapy); the mean follow-up period was 510.9 days.
• At 12 months, there was no significant difference in the percent TBWL among patients receiving the GLP-1 monotherapy or combination therapy (9.6% TBWL in both).
• However, when patients were stratified by their initial GLP-1 response, combination therapy led to a greater percent TBWL than monotherapy in both responders (P = .002) and nonresponders (P < .0001).
• After the addition of bupropion/naltrexone, the mean percent TBWL was 4.3% (P < .001) and 5.3% (P = .009) at 6 and 12 months, respectively, among the responders, and 3.7% (P = .009) and 4.0% (P = .02) at 6 and 12 months, respectively, among the nonresponders.

IN PRACTICE:

“Specific characteristics of individuals who benefit from the bupropion/naltrexone augmentation should be examined to identify patient populations wherein this may be of greatest benefit,” the authors wrote.

SOURCE:

This study, led by James Naude, Faculty of Medicine, University of British Columbia, Vancouver, Canada, was published in the International Journal of Obesity.

LIMITATIONS:

Virtual care and self-reported weights by patients owing to the COVID-19 pandemic could have introduced bias. Some of the data on weight and medication adherence were missing. Moreover, there was no placebo control; hence, there may be confounding by indication.

DISCLOSURES:

The study was not supported by any specific funding. Two of the authors reported receiving educational grants and speaker fees, with one currently being an advisory board member to various pharma companies and the other an advisory board member to a pharma company in the past.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of bupropion/naltrexone to glucagon-like peptide 1 (GLP-1) receptor agonists leads to a further 4%-5% total body weight loss (TBWL) in patients with obesity, including those who show a poor response to initial GLP-1 monotherapy.

METHODOLOGY:

• Some patients with obesity experience suboptimal weight loss with GLP-1 monotherapy; however, adding treatments targeting multiple pathways may offer synergistic effects and improve outcomes.
• Researchers retrospectively evaluated adult patients with body mass index (BMI) ≥ 30 who attended an obesity clinic in Vancouver, Canada, and received a GLP-1 receptor agonist (liraglutide or semaglutide) for at least 6 months.
• They compared patients who continued receiving GLP-1 monotherapy with those who received add-on bupropion/naltrexone (combination therapy).
• The percent TBWL was compared between the groups from the initiation of the GLP-1 or the addition of bupropion/naltrexone over a period of 6 and 12 months.
• Patients prescribed combination therapy were stratified into responders (≥ 5% TBWL) and nonresponders (< 5% TBWL) based on their initial response to GLP-1 monotherapy.

TAKEAWAY:

• Researchers included 415 patients with BMI ≥ 30 (mean age, 47.3 years; 75.6% women), of whom 320 continued receiving GLP-1 monotherapy and 95 received add-on bupropion/naltrexone (combination therapy); the mean follow-up period was 510.9 days.
• At 12 months, there was no significant difference in the percent TBWL among patients receiving the GLP-1 monotherapy or combination therapy (9.6% TBWL in both).
• However, when patients were stratified by their initial GLP-1 response, combination therapy led to a greater percent TBWL than monotherapy in both responders (P = .002) and nonresponders (P < .0001).
• After the addition of bupropion/naltrexone, the mean percent TBWL was 4.3% (P < .001) and 5.3% (P = .009) at 6 and 12 months, respectively, among the responders, and 3.7% (P = .009) and 4.0% (P = .02) at 6 and 12 months, respectively, among the nonresponders.

IN PRACTICE:

“Specific characteristics of individuals who benefit from the bupropion/naltrexone augmentation should be examined to identify patient populations wherein this may be of greatest benefit,” the authors wrote.

SOURCE:

This study, led by James Naude, Faculty of Medicine, University of British Columbia, Vancouver, Canada, was published in the International Journal of Obesity.

LIMITATIONS:

Virtual care and self-reported weights by patients owing to the COVID-19 pandemic could have introduced bias. Some of the data on weight and medication adherence were missing. Moreover, there was no placebo control; hence, there may be confounding by indication.

DISCLOSURES:

The study was not supported by any specific funding. Two of the authors reported receiving educational grants and speaker fees, with one currently being an advisory board member to various pharma companies and the other an advisory board member to a pharma company in the past.

A version of this article appeared on Medscape.com.

TOPLINE:

In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).

METHODOLOGY:

• Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
• This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
• Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
• GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
• CGM-derived glycemic patterns were compared between the participants with and without GDM.

TAKEAWAY:

• Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
• Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
• The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
• Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.

IN PRACTICE:

“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”

SOURCE:

The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.

LIMITATIONS:

To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.

DISCLOSURES:

The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.

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

TOPLINE:

In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).

METHODOLOGY:

• Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
• This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
• Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
• GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
• CGM-derived glycemic patterns were compared between the participants with and without GDM.

TAKEAWAY:

• Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
• Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
• The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
• Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.

IN PRACTICE:

“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”

SOURCE:

The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.

LIMITATIONS:

To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.

DISCLOSURES:

The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.

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

TOPLINE:

In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).

METHODOLOGY:

• Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
• This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
• Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
• GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
• CGM-derived glycemic patterns were compared between the participants with and without GDM.

TAKEAWAY:

• Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
• Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
• The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
• Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.

IN PRACTICE:

“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”

SOURCE:

The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.

LIMITATIONS:

To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.

DISCLOSURES:

The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.

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

NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.

As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.

Several drugs in various stages of development are aimed at preserving or building muscle mass and boosting fat loss when used in combination with one of these medications for weight loss. Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.

One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.

Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.

Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.

Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.

“Wouldn’t it be nice if there was a drug that built up muscle mass?”

Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.

The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”

Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”

The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”

And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”

“We have to also focus on ‘first, do no harm’”

Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”

Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.

“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”

“Wherever the GLP-1s go, we go”

In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”

Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
 

A version of this article appeared on Medscape.com.

NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.

As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.

Several drugs in various stages of development are aimed at preserving or building muscle mass and boosting fat loss when used in combination with one of these medications for weight loss. Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.

One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.

Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.

Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.

Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.

“Wouldn’t it be nice if there was a drug that built up muscle mass?”

Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.

The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”

Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”

The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”

And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”

“We have to also focus on ‘first, do no harm’”

Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”

Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.

“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”

“Wherever the GLP-1s go, we go”

In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”

Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
 

A version of this article appeared on Medscape.com.

NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.

As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.

Several drugs in various stages of development are aimed at preserving or building muscle mass and boosting fat loss when used in combination with one of these medications for weight loss. Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.

One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.

Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.

Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.

Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.

“Wouldn’t it be nice if there was a drug that built up muscle mass?”

Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.

The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”

Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”

The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”

And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”

“We have to also focus on ‘first, do no harm’”

Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”

Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.

“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”

“Wherever the GLP-1s go, we go”

In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”

Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
 

A version of this article appeared on Medscape.com.

Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.

Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.

The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.

A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.

Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).

Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).

As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.

The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
 

Data Add to Awareness of Risk Factors

The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.  

The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.

The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.

Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.

The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.

Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.

Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.

The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.

A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.

Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).

Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).

As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.

The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
 

Data Add to Awareness of Risk Factors

The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.  

The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.

The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.

Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.

The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.

Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.

Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.

The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.

A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.

Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).

Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).

As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.

The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
 

Data Add to Awareness of Risk Factors

The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.  

The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.

The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.

Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.

The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.

Artificial intelligence (AI) has drawn interest in ophthalmology for its potential to track disease trends in huge populations, such as the 38.4 million people in the United States with diabetes who are at risk for diabetic eye disease. However, a recent study using AI to detect diabetic retinopathy from retinal photo screenings has found wide disparities in the quality of data being fed into the algorithm.

And screening photos captured in nine primary care settings were three times more likely to be unusable than those obtained in two ophthalmology clinics, a study at Temple University in Philadelphia found. The results of the new research were reported at the Association for Research in Vision and Ophthalmology (ARVO) 2024 annual meeting.

“AI-assisted diabetic retinopathy screenings were more successful when completed in the ophthalmology clinic setting compared to the primary care setting,” study leader Madelyn Class, a medical student at Temple, told this news organization. One key difference, Ms. Class said, was that the specialty clinics used a photographer training in capturing ophthalmic images, while the primary care sites had medical assistants taking the photos.
 

Challenges of Screening in Primary Care

The American Diabetes Association acknowledged in a 2017 position statement that retinal photography has the potential to bring screening into settings where optometrists or ophthalmologists are unavailable. This study showed the potential may not yet be realized.

In the primary care setting, 42.5% of retinal photos were ungradable compared with 14.5% in the specialty settings.

The number of patients diagnosed with more-than-mild diabetic retinopathy also varied significantly between the two settings — 13% in primary care and 24% in ophthalmology — as did the rates of follow-up appointments: 58% and 80%, respectively.

“It seems user error played a role in the quality of photographs that were taken,” Ms. Class said. “Some of the images we received from the primary care settings were actually of the eyelid, or even the curtains on the wall, rather than the fundus.

“All the camera operators in the study received training on the imaging device,” Ms. Class added. “This suggests that some of the photographers were rushed, out of practice, or simply no longer interested in taking photos,” she said. “Apparently, we will have to continuously monitor the performance of each photographer to ensure that quality photos are being taken.”

The findings may also point to the need for using different equipment for screening in primary care, Ms. Class added. “Robotic as opposed to manual cameras may help eliminate some of the user error that was experienced with primary care screenings,” she said.

Need for Training ‘Fixable’

These findings demonstrate the challenges of capturing usable retinal images outside of an eye care professional’s office, according to Jennifer Lim, MD, director of the retina service at the University of Illinois Chicago.

“This study illustrates that implementation is the rub of AI,” Dr. Lim told this news organization. “Getting primary care doctors and clinics to want to adopt and figure out how to implement AI screening [for diabetic retinopathy] in a healthcare system is difficult, so I applaud the Temple University system for trying to integrate retinal photography-based AI screening into the primary care outpatient centers and comparing outcomes to the ophthalmology clinics.”

The study showed that photographers need not only initial training but also monitoring to avoid ungradable images, Dr. Lim added, a problem that is “fixable.”

“It’s going to take a lot of work to get the message out to the primary care practices that these autonomous, cloud-based systems are available and effective for detecting retinopathy,” she said.

But the effort is worth it, she added: “It doesn’t take much time to take these photos for diabetic retinopathy screening, and the potential benefits are huge because the earlier you diagnose diabetic retinopathy that’s more than mild, the more likely the patient can be sent for eye care in a timely fashion and thus prevent visual loss from diabetic retinopathy.”

Ms. Class had no relevant disclosures. Dr. Lim disclosed a past relationship with Eyenuk, the maker of retinal screening cameras.

A version of this article appeared on Medscape.com .

Artificial intelligence (AI) has drawn interest in ophthalmology for its potential to track disease trends in huge populations, such as the 38.4 million people in the United States with diabetes who are at risk for diabetic eye disease. However, a recent study using AI to detect diabetic retinopathy from retinal photo screenings has found wide disparities in the quality of data being fed into the algorithm.

And screening photos captured in nine primary care settings were three times more likely to be unusable than those obtained in two ophthalmology clinics, a study at Temple University in Philadelphia found. The results of the new research were reported at the Association for Research in Vision and Ophthalmology (ARVO) 2024 annual meeting.

“AI-assisted diabetic retinopathy screenings were more successful when completed in the ophthalmology clinic setting compared to the primary care setting,” study leader Madelyn Class, a medical student at Temple, told this news organization. One key difference, Ms. Class said, was that the specialty clinics used a photographer training in capturing ophthalmic images, while the primary care sites had medical assistants taking the photos.
 

Challenges of Screening in Primary Care

The American Diabetes Association acknowledged in a 2017 position statement that retinal photography has the potential to bring screening into settings where optometrists or ophthalmologists are unavailable. This study showed the potential may not yet be realized.

In the primary care setting, 42.5% of retinal photos were ungradable compared with 14.5% in the specialty settings.

The number of patients diagnosed with more-than-mild diabetic retinopathy also varied significantly between the two settings — 13% in primary care and 24% in ophthalmology — as did the rates of follow-up appointments: 58% and 80%, respectively.

“It seems user error played a role in the quality of photographs that were taken,” Ms. Class said. “Some of the images we received from the primary care settings were actually of the eyelid, or even the curtains on the wall, rather than the fundus.

“All the camera operators in the study received training on the imaging device,” Ms. Class added. “This suggests that some of the photographers were rushed, out of practice, or simply no longer interested in taking photos,” she said. “Apparently, we will have to continuously monitor the performance of each photographer to ensure that quality photos are being taken.”

The findings may also point to the need for using different equipment for screening in primary care, Ms. Class added. “Robotic as opposed to manual cameras may help eliminate some of the user error that was experienced with primary care screenings,” she said.

Need for Training ‘Fixable’

These findings demonstrate the challenges of capturing usable retinal images outside of an eye care professional’s office, according to Jennifer Lim, MD, director of the retina service at the University of Illinois Chicago.

“This study illustrates that implementation is the rub of AI,” Dr. Lim told this news organization. “Getting primary care doctors and clinics to want to adopt and figure out how to implement AI screening [for diabetic retinopathy] in a healthcare system is difficult, so I applaud the Temple University system for trying to integrate retinal photography-based AI screening into the primary care outpatient centers and comparing outcomes to the ophthalmology clinics.”

The study showed that photographers need not only initial training but also monitoring to avoid ungradable images, Dr. Lim added, a problem that is “fixable.”

“It’s going to take a lot of work to get the message out to the primary care practices that these autonomous, cloud-based systems are available and effective for detecting retinopathy,” she said.

But the effort is worth it, she added: “It doesn’t take much time to take these photos for diabetic retinopathy screening, and the potential benefits are huge because the earlier you diagnose diabetic retinopathy that’s more than mild, the more likely the patient can be sent for eye care in a timely fashion and thus prevent visual loss from diabetic retinopathy.”

Ms. Class had no relevant disclosures. Dr. Lim disclosed a past relationship with Eyenuk, the maker of retinal screening cameras.

A version of this article appeared on Medscape.com .

Artificial intelligence (AI) has drawn interest in ophthalmology for its potential to track disease trends in huge populations, such as the 38.4 million people in the United States with diabetes who are at risk for diabetic eye disease. However, a recent study using AI to detect diabetic retinopathy from retinal photo screenings has found wide disparities in the quality of data being fed into the algorithm.

And screening photos captured in nine primary care settings were three times more likely to be unusable than those obtained in two ophthalmology clinics, a study at Temple University in Philadelphia found. The results of the new research were reported at the Association for Research in Vision and Ophthalmology (ARVO) 2024 annual meeting.

“AI-assisted diabetic retinopathy screenings were more successful when completed in the ophthalmology clinic setting compared to the primary care setting,” study leader Madelyn Class, a medical student at Temple, told this news organization. One key difference, Ms. Class said, was that the specialty clinics used a photographer training in capturing ophthalmic images, while the primary care sites had medical assistants taking the photos.
 

Challenges of Screening in Primary Care

The American Diabetes Association acknowledged in a 2017 position statement that retinal photography has the potential to bring screening into settings where optometrists or ophthalmologists are unavailable. This study showed the potential may not yet be realized.

In the primary care setting, 42.5% of retinal photos were ungradable compared with 14.5% in the specialty settings.

The number of patients diagnosed with more-than-mild diabetic retinopathy also varied significantly between the two settings — 13% in primary care and 24% in ophthalmology — as did the rates of follow-up appointments: 58% and 80%, respectively.

“It seems user error played a role in the quality of photographs that were taken,” Ms. Class said. “Some of the images we received from the primary care settings were actually of the eyelid, or even the curtains on the wall, rather than the fundus.

“All the camera operators in the study received training on the imaging device,” Ms. Class added. “This suggests that some of the photographers were rushed, out of practice, or simply no longer interested in taking photos,” she said. “Apparently, we will have to continuously monitor the performance of each photographer to ensure that quality photos are being taken.”

The findings may also point to the need for using different equipment for screening in primary care, Ms. Class added. “Robotic as opposed to manual cameras may help eliminate some of the user error that was experienced with primary care screenings,” she said.

Need for Training ‘Fixable’

These findings demonstrate the challenges of capturing usable retinal images outside of an eye care professional’s office, according to Jennifer Lim, MD, director of the retina service at the University of Illinois Chicago.

“This study illustrates that implementation is the rub of AI,” Dr. Lim told this news organization. “Getting primary care doctors and clinics to want to adopt and figure out how to implement AI screening [for diabetic retinopathy] in a healthcare system is difficult, so I applaud the Temple University system for trying to integrate retinal photography-based AI screening into the primary care outpatient centers and comparing outcomes to the ophthalmology clinics.”

The study showed that photographers need not only initial training but also monitoring to avoid ungradable images, Dr. Lim added, a problem that is “fixable.”

“It’s going to take a lot of work to get the message out to the primary care practices that these autonomous, cloud-based systems are available and effective for detecting retinopathy,” she said.

But the effort is worth it, she added: “It doesn’t take much time to take these photos for diabetic retinopathy screening, and the potential benefits are huge because the earlier you diagnose diabetic retinopathy that’s more than mild, the more likely the patient can be sent for eye care in a timely fashion and thus prevent visual loss from diabetic retinopathy.”

Ms. Class had no relevant disclosures. Dr. Lim disclosed a past relationship with Eyenuk, the maker of retinal screening cameras.

A version of this article appeared on Medscape.com .

TOPLINE:

Various food additive emulsifiers, including total carrageenans, carrageenan gum, tripotassium phosphate, sodium citrate, and guar gum, can increase the risk for type 2 diabetes (T2D), showed a recent study.

METHODOLOGY:

• Food emulsifiers, which are extensively used to enhance the texture and improve the shelf life of various ultraprocessed food items, have been shown to increase the risk for cardiovascular disease and cancer.
• In this study, the dietary intake data of 104,139 adults (79.2% women; mean age, 42.7 years) enrolled in the French NutriNet-Santé prospective cohort study from May 2009 to April 2023 were assessed for 24 hours on 3 nonconsecutive days at inclusion and every 6 months thereafter to determine the risk for T2D.
• The dietary records of participants, which were linked to food composition databases, were used to quantify the food additive intake.
• T2D cases were identified using a multisource approach encompassing self-reports, health questionnaires, national health insurance system databases, and/or mortality registries.

TAKEAWAY:

• During a mean follow-up period of 6.8 years, 1056 incident cases of T2D were reported.
• Almost all (99.7%) participants were exposed to at least one food additive emulsifier, with the main contributors being ultraprocessed fruits and vegetables (18.5%), cakes and biscuits (14.7%), and dairy products (10.0%).
• The intake of the following emulsifiers increased the risk for T2D:
• Total carrageenans and carrageenan gum (3% increased risk per increment of 100 mg/d; P < .001)
• Tripotassium phosphate (15% increased risk per increment of 500 mg/d; P = .023)
• Acetyl tartaric acid esters of monoglycerides and diglycerides of fatty acids (4% increased risk per increment of 100 mg/d; P = .042)
• Sodium citrate (4% increased risk per increment of 500 mg/d; P = .008)
• Guar gum (11% increased risk per increment of 500 mg/d; P < .0001)
• Gum arabic (3% increased risk per increment of 1000 mg/d; P = .013)
• Xanthan gum (8% increased risk per increment of 500 mg/d; P = .013)

IN PRACTICE:

In an accompanying commentary, experts postulated that “findings from this and other studies could prompt regulatory agencies and policymakers to reconsider the rules governing the use of emulsifiers and other additives by the food industry such as setting limits and requiring better disclosure of food additive contents to help consumers make more informed choices.”

SOURCE:

Clara Salame, PhD, Université Sorbonne Paris Nord and Université Paris Cité, INSERM, INRAE, CNAM, Center of Research in Epidemiology and Statistics, Nutritional Epidemiology Research Team, Paris, France, led this study, which was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The observational nature of this study is not sufficient to establish causality relationships. There may have been measurement errors in emulsifier exposure, particularly in products exempted from labeling requirements. This cohort’s demographics, which included a higher percentage of women and a health-conscious population, may affect the generalizability of the study’s findings.

DISCLOSURES:

This study received funding from the European Research Council, and the NutriNet-Santé study was supported by many public institutions such as the Ministère de la Santé, Santé publique France, Université Sorbonne Paris Nord, and others. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Various food additive emulsifiers, including total carrageenans, carrageenan gum, tripotassium phosphate, sodium citrate, and guar gum, can increase the risk for type 2 diabetes (T2D), showed a recent study.

METHODOLOGY:

• Food emulsifiers, which are extensively used to enhance the texture and improve the shelf life of various ultraprocessed food items, have been shown to increase the risk for cardiovascular disease and cancer.
• In this study, the dietary intake data of 104,139 adults (79.2% women; mean age, 42.7 years) enrolled in the French NutriNet-Santé prospective cohort study from May 2009 to April 2023 were assessed for 24 hours on 3 nonconsecutive days at inclusion and every 6 months thereafter to determine the risk for T2D.
• The dietary records of participants, which were linked to food composition databases, were used to quantify the food additive intake.
• T2D cases were identified using a multisource approach encompassing self-reports, health questionnaires, national health insurance system databases, and/or mortality registries.

TAKEAWAY:

• During a mean follow-up period of 6.8 years, 1056 incident cases of T2D were reported.
• Almost all (99.7%) participants were exposed to at least one food additive emulsifier, with the main contributors being ultraprocessed fruits and vegetables (18.5%), cakes and biscuits (14.7%), and dairy products (10.0%).
• The intake of the following emulsifiers increased the risk for T2D:
• Total carrageenans and carrageenan gum (3% increased risk per increment of 100 mg/d; P < .001)
• Tripotassium phosphate (15% increased risk per increment of 500 mg/d; P = .023)
• Acetyl tartaric acid esters of monoglycerides and diglycerides of fatty acids (4% increased risk per increment of 100 mg/d; P = .042)
• Sodium citrate (4% increased risk per increment of 500 mg/d; P = .008)
• Guar gum (11% increased risk per increment of 500 mg/d; P < .0001)
• Gum arabic (3% increased risk per increment of 1000 mg/d; P = .013)
• Xanthan gum (8% increased risk per increment of 500 mg/d; P = .013)

IN PRACTICE:

In an accompanying commentary, experts postulated that “findings from this and other studies could prompt regulatory agencies and policymakers to reconsider the rules governing the use of emulsifiers and other additives by the food industry such as setting limits and requiring better disclosure of food additive contents to help consumers make more informed choices.”

SOURCE:

Clara Salame, PhD, Université Sorbonne Paris Nord and Université Paris Cité, INSERM, INRAE, CNAM, Center of Research in Epidemiology and Statistics, Nutritional Epidemiology Research Team, Paris, France, led this study, which was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The observational nature of this study is not sufficient to establish causality relationships. There may have been measurement errors in emulsifier exposure, particularly in products exempted from labeling requirements. This cohort’s demographics, which included a higher percentage of women and a health-conscious population, may affect the generalizability of the study’s findings.

DISCLOSURES:

This study received funding from the European Research Council, and the NutriNet-Santé study was supported by many public institutions such as the Ministère de la Santé, Santé publique France, Université Sorbonne Paris Nord, and others. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Various food additive emulsifiers, including total carrageenans, carrageenan gum, tripotassium phosphate, sodium citrate, and guar gum, can increase the risk for type 2 diabetes (T2D), showed a recent study.

METHODOLOGY:

• Food emulsifiers, which are extensively used to enhance the texture and improve the shelf life of various ultraprocessed food items, have been shown to increase the risk for cardiovascular disease and cancer.
• In this study, the dietary intake data of 104,139 adults (79.2% women; mean age, 42.7 years) enrolled in the French NutriNet-Santé prospective cohort study from May 2009 to April 2023 were assessed for 24 hours on 3 nonconsecutive days at inclusion and every 6 months thereafter to determine the risk for T2D.
• The dietary records of participants, which were linked to food composition databases, were used to quantify the food additive intake.
• T2D cases were identified using a multisource approach encompassing self-reports, health questionnaires, national health insurance system databases, and/or mortality registries.

TAKEAWAY:

• During a mean follow-up period of 6.8 years, 1056 incident cases of T2D were reported.
• Almost all (99.7%) participants were exposed to at least one food additive emulsifier, with the main contributors being ultraprocessed fruits and vegetables (18.5%), cakes and biscuits (14.7%), and dairy products (10.0%).
• The intake of the following emulsifiers increased the risk for T2D:
• Total carrageenans and carrageenan gum (3% increased risk per increment of 100 mg/d; P < .001)
• Tripotassium phosphate (15% increased risk per increment of 500 mg/d; P = .023)
• Acetyl tartaric acid esters of monoglycerides and diglycerides of fatty acids (4% increased risk per increment of 100 mg/d; P = .042)
• Sodium citrate (4% increased risk per increment of 500 mg/d; P = .008)
• Guar gum (11% increased risk per increment of 500 mg/d; P < .0001)
• Gum arabic (3% increased risk per increment of 1000 mg/d; P = .013)
• Xanthan gum (8% increased risk per increment of 500 mg/d; P = .013)

IN PRACTICE:

In an accompanying commentary, experts postulated that “findings from this and other studies could prompt regulatory agencies and policymakers to reconsider the rules governing the use of emulsifiers and other additives by the food industry such as setting limits and requiring better disclosure of food additive contents to help consumers make more informed choices.”

SOURCE:

Clara Salame, PhD, Université Sorbonne Paris Nord and Université Paris Cité, INSERM, INRAE, CNAM, Center of Research in Epidemiology and Statistics, Nutritional Epidemiology Research Team, Paris, France, led this study, which was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The observational nature of this study is not sufficient to establish causality relationships. There may have been measurement errors in emulsifier exposure, particularly in products exempted from labeling requirements. This cohort’s demographics, which included a higher percentage of women and a health-conscious population, may affect the generalizability of the study’s findings.

DISCLOSURES:

This study received funding from the European Research Council, and the NutriNet-Santé study was supported by many public institutions such as the Ministère de la Santé, Santé publique France, Université Sorbonne Paris Nord, and others. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Eli Lilly has announced positive phase 3 top-line results for its once-weekly insulin efsitora alfa (efsitora) in insulin-naive adults with type 2 diabetes and those who require multiple daily insulin injections.

The new data come from the company’s QWINT-2 and QWINT-4 phase 3 clinical trials. In both, efsitora was noninferior to daily basal insulin in lowering A1c. The comparator was once-daily degludec in QUINT-2 and glargine in QUINT-4.

These results come days before the once-weekly competitor, Novo Nordisk’s insulin icodec, will be discussed by the US Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee. On May 24, 2024, the panel will review safety and efficacy of icodec for the proposed indication of improving glycemic control in adults with diabetes.
 

Hypoglycemia and Affordability Are Concerns

Asked to comment, Anne L. Peters, MD, director of the University of Southern California Westside Center for Diabetes, Los Angeles, told this news organization that she’s “cautiously optimistic” about once-weekly insulin. “I honestly think it’s going to have an important role in diabetes. … And I’m looking forward to learning how it’s going to help my patients.”

However, Dr. Peters also said she’s concerned about the possible risk for hypoglycemia with long-acting insulin, particularly in patients with variable schedules. “The real fear they have and I have is hypoglycemia. That being said, I think that it will be great for some patients where hypoglycemia is less of a concern, and they’re in a more stable environment. … I think there are patients who will really benefit but I have to figure out who those patients are.”

Dr. Peters, who takes care of many low-income patients, also pointed out that once approved, these newer insulins may not be affordable for those who could most benefit from them in terms of improved adherence. Insurance plans may not cover them initially, especially given that the data thus far show noninferiority, not superiority, to daily basal. “The patients in whom I would like to use it most are the patients who have the most trouble with social determinants of health and other issues. I really think it could really make a difference for them, but it won’t get there for a while.”

And, she noted, titrating doses of once-weekly insulin will likely come with a learning curve. “Having spent a lifetime adjusting basal insulin on a daily basis to suddenly do it on a weekly basis, as a diabetologist I’m going to have to get used to what that feels like.”
 

Topline Data Show Noninferiority to Daily Basal Insulin

In QWINT-2, efficacy and safety of once-weekly efsitora was compared with those of once-daily insulin degludec for 52 weeks. Study participants were all new to using insulin, but some were using glucagon-like peptide 1 receptor agonists.

The treat-to-target trial met its primary noninferiority endpoint for hemoglobin A1c reduction at week 52. A1c values were lowered by 1.34 percentage points with efsitora compared with 1.26 for insulin degludec, resulting in non–significantly different A1c values of 6.87% and 6.95%, respectively.

In QWINT-4, efficacy and safety of once-weekly efsitora was compared with those of daily insulin glargine for 26 weeks in adults with type 2 diabetes who had previously been treated with basal insulin and at least two injections of premeal insulin per day. Participants were randomized to receive efsitora once weekly or insulin glargine once daily, and both groups used lispro before meals.

This trial also met its primary endpoint, with both reducing A1c by 1.07 percentage points at 26 weeks, resulting in levels of 7.12% and 7.11%, respectively.

The full results for QWINT-2 will be presented at the European Association for the Study of Diabetes meeting this September.

Dr. Peters served on the advisory board for Abbott Diabetes Care; Becton Dickinson; Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Lexicon Pharmaceuticals, Inc.; Livongo; Medscape Medical News; Merck & Co., Inc.; Novo Nordisk; Omada Health; OptumHealth; Sanofi; and Zafgen. She received research support from Dexcom, MannKind Corporation, and Astra Zeneca and served as a member of a speakers bureau for Novo Nordisk.

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

Eli Lilly has announced positive phase 3 top-line results for its once-weekly insulin efsitora alfa (efsitora) in insulin-naive adults with type 2 diabetes and those who require multiple daily insulin injections.

The new data come from the company’s QWINT-2 and QWINT-4 phase 3 clinical trials. In both, efsitora was noninferior to daily basal insulin in lowering A1c. The comparator was once-daily degludec in QUINT-2 and glargine in QUINT-4.

These results come days before the once-weekly competitor, Novo Nordisk’s insulin icodec, will be discussed by the US Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee. On May 24, 2024, the panel will review safety and efficacy of icodec for the proposed indication of improving glycemic control in adults with diabetes.
 

Hypoglycemia and Affordability Are Concerns

Asked to comment, Anne L. Peters, MD, director of the University of Southern California Westside Center for Diabetes, Los Angeles, told this news organization that she’s “cautiously optimistic” about once-weekly insulin. “I honestly think it’s going to have an important role in diabetes. … And I’m looking forward to learning how it’s going to help my patients.”

However, Dr. Peters also said she’s concerned about the possible risk for hypoglycemia with long-acting insulin, particularly in patients with variable schedules. “The real fear they have and I have is hypoglycemia. That being said, I think that it will be great for some patients where hypoglycemia is less of a concern, and they’re in a more stable environment. … I think there are patients who will really benefit but I have to figure out who those patients are.”

Dr. Peters, who takes care of many low-income patients, also pointed out that once approved, these newer insulins may not be affordable for those who could most benefit from them in terms of improved adherence. Insurance plans may not cover them initially, especially given that the data thus far show noninferiority, not superiority, to daily basal. “The patients in whom I would like to use it most are the patients who have the most trouble with social determinants of health and other issues. I really think it could really make a difference for them, but it won’t get there for a while.”

And, she noted, titrating doses of once-weekly insulin will likely come with a learning curve. “Having spent a lifetime adjusting basal insulin on a daily basis to suddenly do it on a weekly basis, as a diabetologist I’m going to have to get used to what that feels like.”
 

Topline Data Show Noninferiority to Daily Basal Insulin

In QWINT-2, efficacy and safety of once-weekly efsitora was compared with those of once-daily insulin degludec for 52 weeks. Study participants were all new to using insulin, but some were using glucagon-like peptide 1 receptor agonists.

The treat-to-target trial met its primary noninferiority endpoint for hemoglobin A1c reduction at week 52. A1c values were lowered by 1.34 percentage points with efsitora compared with 1.26 for insulin degludec, resulting in non–significantly different A1c values of 6.87% and 6.95%, respectively.

In QWINT-4, efficacy and safety of once-weekly efsitora was compared with those of daily insulin glargine for 26 weeks in adults with type 2 diabetes who had previously been treated with basal insulin and at least two injections of premeal insulin per day. Participants were randomized to receive efsitora once weekly or insulin glargine once daily, and both groups used lispro before meals.

This trial also met its primary endpoint, with both reducing A1c by 1.07 percentage points at 26 weeks, resulting in levels of 7.12% and 7.11%, respectively.

The full results for QWINT-2 will be presented at the European Association for the Study of Diabetes meeting this September.

Dr. Peters served on the advisory board for Abbott Diabetes Care; Becton Dickinson; Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Lexicon Pharmaceuticals, Inc.; Livongo; Medscape Medical News; Merck & Co., Inc.; Novo Nordisk; Omada Health; OptumHealth; Sanofi; and Zafgen. She received research support from Dexcom, MannKind Corporation, and Astra Zeneca and served as a member of a speakers bureau for Novo Nordisk.

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

Eli Lilly has announced positive phase 3 top-line results for its once-weekly insulin efsitora alfa (efsitora) in insulin-naive adults with type 2 diabetes and those who require multiple daily insulin injections.

The new data come from the company’s QWINT-2 and QWINT-4 phase 3 clinical trials. In both, efsitora was noninferior to daily basal insulin in lowering A1c. The comparator was once-daily degludec in QUINT-2 and glargine in QUINT-4.

These results come days before the once-weekly competitor, Novo Nordisk’s insulin icodec, will be discussed by the US Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee. On May 24, 2024, the panel will review safety and efficacy of icodec for the proposed indication of improving glycemic control in adults with diabetes.
 

Hypoglycemia and Affordability Are Concerns

Asked to comment, Anne L. Peters, MD, director of the University of Southern California Westside Center for Diabetes, Los Angeles, told this news organization that she’s “cautiously optimistic” about once-weekly insulin. “I honestly think it’s going to have an important role in diabetes. … And I’m looking forward to learning how it’s going to help my patients.”

However, Dr. Peters also said she’s concerned about the possible risk for hypoglycemia with long-acting insulin, particularly in patients with variable schedules. “The real fear they have and I have is hypoglycemia. That being said, I think that it will be great for some patients where hypoglycemia is less of a concern, and they’re in a more stable environment. … I think there are patients who will really benefit but I have to figure out who those patients are.”

Dr. Peters, who takes care of many low-income patients, also pointed out that once approved, these newer insulins may not be affordable for those who could most benefit from them in terms of improved adherence. Insurance plans may not cover them initially, especially given that the data thus far show noninferiority, not superiority, to daily basal. “The patients in whom I would like to use it most are the patients who have the most trouble with social determinants of health and other issues. I really think it could really make a difference for them, but it won’t get there for a while.”

And, she noted, titrating doses of once-weekly insulin will likely come with a learning curve. “Having spent a lifetime adjusting basal insulin on a daily basis to suddenly do it on a weekly basis, as a diabetologist I’m going to have to get used to what that feels like.”
 

Topline Data Show Noninferiority to Daily Basal Insulin

In QWINT-2, efficacy and safety of once-weekly efsitora was compared with those of once-daily insulin degludec for 52 weeks. Study participants were all new to using insulin, but some were using glucagon-like peptide 1 receptor agonists.

The treat-to-target trial met its primary noninferiority endpoint for hemoglobin A1c reduction at week 52. A1c values were lowered by 1.34 percentage points with efsitora compared with 1.26 for insulin degludec, resulting in non–significantly different A1c values of 6.87% and 6.95%, respectively.

In QWINT-4, efficacy and safety of once-weekly efsitora was compared with those of daily insulin glargine for 26 weeks in adults with type 2 diabetes who had previously been treated with basal insulin and at least two injections of premeal insulin per day. Participants were randomized to receive efsitora once weekly or insulin glargine once daily, and both groups used lispro before meals.

This trial also met its primary endpoint, with both reducing A1c by 1.07 percentage points at 26 weeks, resulting in levels of 7.12% and 7.11%, respectively.

The full results for QWINT-2 will be presented at the European Association for the Study of Diabetes meeting this September.

Dr. Peters served on the advisory board for Abbott Diabetes Care; Becton Dickinson; Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Lexicon Pharmaceuticals, Inc.; Livongo; Medscape Medical News; Merck & Co., Inc.; Novo Nordisk; Omada Health; OptumHealth; Sanofi; and Zafgen. She received research support from Dexcom, MannKind Corporation, and Astra Zeneca and served as a member of a speakers bureau for Novo Nordisk.

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

Serious mental illness (SMI), including bipolar disorder or schizophrenia spectrum disorders, is associated with a twofold increased risk for comorbid physical illness, results of a new meta-analysis showed.

“Although treatment of physical and mental health remains siloed in many health services globally, the high prevalence of physical multimorbidity attests to the urgent need for integrated care models that address both physical and mental health outcomes in people with severe mental illness,” the authors, led by Sean Halstead, MD, of The University of Queensland Medical School in Brisbane, Australia, wrote.

The findings were published online in The Lancet Psychiatry.
 

Shorter Lifespan?

SMI is associated with reduced life expectancy, and experts speculate that additional chronic illnesses — whether physical or psychiatric — may underlie this association.

While previous research has paired SMI with comorbid physical illnesses, the researchers noted that this study is the first to focus on both physical and psychiatric multimorbidity in individuals with SMI.

The investigators conducted a meta-analysis of 82 observational studies comprising 1.6 million individuals with SMI and 13.2 million control subjects to determine the risk for physical or psychiatric multimorbidity.

Studies were included if participants were diagnosed with either a schizophrenia spectrum disorder or bipolar disorder, and the study assessed either physical multimorbidity (at least two physical health conditions) or psychiatric multimorbidity (at least three psychiatric conditions), including the initial SMI.

Investigators found that individuals with SMI had more than a twofold increased risk for physical multimorbidity than those without SMI (odds ratio [OR], 2.40; 95% CI, 1.57-3.65; P = .0009).

Physical multimorbidity, which included cardiovascular, endocrine, neurological rental, gastrointestinal, musculoskeletal, and infectious disorders, was prevalent at similar rates in both schizophrenia spectrum disorder and bipolar disorder.

The ratio of physical multimorbidity was about four times higher in younger populations with SMI (mean age ≤ 40; OR, 3.99; 95% CI, 1.43-11.10) than in older populations (mean age > 40; OR, 1.55; 95% CI, 0.96-2.51; subgroup differences, P = .0013).

In terms of absolute prevalence, 25% of those with SMI had a physical multimorbidity, and 14% had a psychiatric multimorbidity, which were primarily anxiety and substance use disorders.

Investigators speculated that physical multimorbidity in SMI could stem from side effects of psychotropic medications, which are known to cause rapid cardiometabolic changes, including weight gain. In addition, lifestyle factors or nonmodifiable risk factors could also contribute to physical multimorbidity.

The study’s limitations included its small sample sizes for subgroup analyses and insufficient analysis for significant covariates, including smoking rates and symptom severity.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” the investigators wrote. They added that a greater understanding of the epidemiological manifestations of multimorbidity in SMI is “imperative.”

There was no source of funding for this study. Dr. Halstead is supported by the Australian Research Training Program scholarship. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

Serious mental illness (SMI), including bipolar disorder or schizophrenia spectrum disorders, is associated with a twofold increased risk for comorbid physical illness, results of a new meta-analysis showed.

“Although treatment of physical and mental health remains siloed in many health services globally, the high prevalence of physical multimorbidity attests to the urgent need for integrated care models that address both physical and mental health outcomes in people with severe mental illness,” the authors, led by Sean Halstead, MD, of The University of Queensland Medical School in Brisbane, Australia, wrote.

The findings were published online in The Lancet Psychiatry.
 

Shorter Lifespan?

SMI is associated with reduced life expectancy, and experts speculate that additional chronic illnesses — whether physical or psychiatric — may underlie this association.

While previous research has paired SMI with comorbid physical illnesses, the researchers noted that this study is the first to focus on both physical and psychiatric multimorbidity in individuals with SMI.

The investigators conducted a meta-analysis of 82 observational studies comprising 1.6 million individuals with SMI and 13.2 million control subjects to determine the risk for physical or psychiatric multimorbidity.

Studies were included if participants were diagnosed with either a schizophrenia spectrum disorder or bipolar disorder, and the study assessed either physical multimorbidity (at least two physical health conditions) or psychiatric multimorbidity (at least three psychiatric conditions), including the initial SMI.

Investigators found that individuals with SMI had more than a twofold increased risk for physical multimorbidity than those without SMI (odds ratio [OR], 2.40; 95% CI, 1.57-3.65; P = .0009).

Physical multimorbidity, which included cardiovascular, endocrine, neurological rental, gastrointestinal, musculoskeletal, and infectious disorders, was prevalent at similar rates in both schizophrenia spectrum disorder and bipolar disorder.

The ratio of physical multimorbidity was about four times higher in younger populations with SMI (mean age ≤ 40; OR, 3.99; 95% CI, 1.43-11.10) than in older populations (mean age > 40; OR, 1.55; 95% CI, 0.96-2.51; subgroup differences, P = .0013).

In terms of absolute prevalence, 25% of those with SMI had a physical multimorbidity, and 14% had a psychiatric multimorbidity, which were primarily anxiety and substance use disorders.

Investigators speculated that physical multimorbidity in SMI could stem from side effects of psychotropic medications, which are known to cause rapid cardiometabolic changes, including weight gain. In addition, lifestyle factors or nonmodifiable risk factors could also contribute to physical multimorbidity.

The study’s limitations included its small sample sizes for subgroup analyses and insufficient analysis for significant covariates, including smoking rates and symptom severity.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” the investigators wrote. They added that a greater understanding of the epidemiological manifestations of multimorbidity in SMI is “imperative.”

There was no source of funding for this study. Dr. Halstead is supported by the Australian Research Training Program scholarship. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

Serious mental illness (SMI), including bipolar disorder or schizophrenia spectrum disorders, is associated with a twofold increased risk for comorbid physical illness, results of a new meta-analysis showed.

“Although treatment of physical and mental health remains siloed in many health services globally, the high prevalence of physical multimorbidity attests to the urgent need for integrated care models that address both physical and mental health outcomes in people with severe mental illness,” the authors, led by Sean Halstead, MD, of The University of Queensland Medical School in Brisbane, Australia, wrote.

The findings were published online in The Lancet Psychiatry.
 

Shorter Lifespan?

SMI is associated with reduced life expectancy, and experts speculate that additional chronic illnesses — whether physical or psychiatric — may underlie this association.

While previous research has paired SMI with comorbid physical illnesses, the researchers noted that this study is the first to focus on both physical and psychiatric multimorbidity in individuals with SMI.

The investigators conducted a meta-analysis of 82 observational studies comprising 1.6 million individuals with SMI and 13.2 million control subjects to determine the risk for physical or psychiatric multimorbidity.

Studies were included if participants were diagnosed with either a schizophrenia spectrum disorder or bipolar disorder, and the study assessed either physical multimorbidity (at least two physical health conditions) or psychiatric multimorbidity (at least three psychiatric conditions), including the initial SMI.

Investigators found that individuals with SMI had more than a twofold increased risk for physical multimorbidity than those without SMI (odds ratio [OR], 2.40; 95% CI, 1.57-3.65; P = .0009).

Physical multimorbidity, which included cardiovascular, endocrine, neurological rental, gastrointestinal, musculoskeletal, and infectious disorders, was prevalent at similar rates in both schizophrenia spectrum disorder and bipolar disorder.

The ratio of physical multimorbidity was about four times higher in younger populations with SMI (mean age ≤ 40; OR, 3.99; 95% CI, 1.43-11.10) than in older populations (mean age > 40; OR, 1.55; 95% CI, 0.96-2.51; subgroup differences, P = .0013).

In terms of absolute prevalence, 25% of those with SMI had a physical multimorbidity, and 14% had a psychiatric multimorbidity, which were primarily anxiety and substance use disorders.

Investigators speculated that physical multimorbidity in SMI could stem from side effects of psychotropic medications, which are known to cause rapid cardiometabolic changes, including weight gain. In addition, lifestyle factors or nonmodifiable risk factors could also contribute to physical multimorbidity.

The study’s limitations included its small sample sizes for subgroup analyses and insufficient analysis for significant covariates, including smoking rates and symptom severity.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” the investigators wrote. They added that a greater understanding of the epidemiological manifestations of multimorbidity in SMI is “imperative.”

There was no source of funding for this study. Dr. Halstead is supported by the Australian Research Training Program scholarship. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com .