GLP-1/glucagon dual agonist linked to 10% weight loss in half of adults with obesity
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Key takeaways:
- About half of adults receiving pemvidutide in a phase 2 trial achieved a 10% or greater weight loss at 24 weeks
- Pemvidutide was associated with reductions in waist circumference, serum lipids and blood pressure
About half of adults taking a novel peptide-based GLP-1/glucagon dual receptor agonist in development for the treatment of obesity in nonalcoholic steatohepatitis lost 10% or more body weight at 24 weeks, according to a press release.
In the MOMENTUM trial, 320 adults with obesity or overweight and at least one comorbidity were randomly assigned to receive either 1.2 mg, 1.8 mg or 2.4 mg pemvidutide (Altimmune) or placebo once a week for 48 weeks. Findings from an interim analysis were released after 160 adults with obesity (median age, 48 years; 75% women; median BMI, 36 kg/m2) completed 24 weeks of treatment.
At 24 weeks, the 1.2 mg pemvidutide group had a mean weight loss of 7.3%, the 1.8 mg group lost 9.4% of their body weight and the 2.4 mg group had a mean weight loss of 10.7% compared with a 1% weight loss for the placebo group (P < .001 for all). Approximately 50% of participants receiving pemvidutide lost 10% or more body weight, and about 20% of those receiving 1.8 mg or 2.4 mg of pemvidutide achieved a 15% or greater weight loss.
Participants with a baseline body weight of 115 kg or less lost a greater proportion of weight. The mean weight loss among those who weighed 115 kg or less at baseline was 8.2% in 1.2 mg pemvidutide group, 10.6% in the 1.8 mg group and 11.9% in the 2.4 mg group compared with 0.8% for those receiving placebo (P < .001).
Adults receiving pemvidutide also had reductions in waist circumference and serum lipids. Clinically meaningful reductions in blood pressure without an increase in heart rate were observed, and glucose homeostasis was maintained.
The majority of adverse events were upper gastrointestinal, such as nausea and vomiting. Most adverse events were mild or moderate, dose-related and similar to what was observed in prior trails, according to the release.
“The weight loss achieved was impressive and bodes well for the effects that could be achieved at the completion of 48 weeks of therapy,” Louis Aronne, MD, Sanford I. Weill Professor of Metabolic Research and professor of clinical medicine at Weill Cornell Medicine, said in the release. “I believe that the reductions in total and LDL cholesterol, blood pressure and waist circumference have the potential to be compelling product attributes, if approved, for patients with risk factors for cardiovascular disease. The impact of baseline weight, which was likewise observed with semaglutide above 115 kg, suggests that higher doses could be an effective strategy in the population with more severe degrees of obesity.”
Rates of adverse events were also low in a phase 1b trial analyzing the safety profile of pemvidutide in adults aged 18 to 65 years with overweight or obesity plus type 2 diabetes. In the trial, 54 participants were randomly assigned to receive 1.2 mg, 1.8 mg or 2.4 mg of pemvidutide or placebo weekly for 12 weeks. All participants used metformin with no or few gastrointestinal symptoms, or an SGLT2 medication for at least 3 months prior to enrollment.
No serious adverse events were observed for any adults receiving pemvidutide, and the rate of gastrointestinal adverse events was low, according to the release. At 12 weeks, the 1.2 mg pemvidutide group lost 4.4% of their body weight, the 1.8 mg group lost 6.1% of their body weight and the 2.4 mg group achieved a 7.7% weight loss. No changes in fasting glucose or HbA1c were observed.
According to the release, the 48-week MOMENTUM phase 2 trial is scheduled to be completed in the fourth quarter of 2023.
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