Pemvidutide Shows Promise: Significant Weight Loss and Muscle Mass Preservation in MOMENTUM Trial

USA: Data from the phase 2 MOMENTUM trial indicate that pemvidutide, a dual GLP-1/Glucagon receptor agonist developed by Altimmune, achieved an average weight reduction of 15.6% in patients with overweight or obesity.

Presented at the 84th American Diabetes Association (ADA) Scientific Sessions, the study findings reveal that pemvidutide led to significant decreases in total body weight, with a unique emphasis on preserving muscle mass. Specifically, the weight loss was attributed to 21.9% lean mass and 78.1% fat reduction.
Dr. Louis J. Aronne, primary investigator from Weill Cornell Medicine’s Comprehensive Weight Control Center, highlighted the implications of these results: “Obesity requires diverse treatment options tailored to individual needs and health conditions. Pemvidutide’s ability to induce substantial weight loss and preserve lean mass is particularly promising.”
These findings were presented in full after an initial 24-week interim analysis by Altimmune in March 2023, where pemvidutide demonstrated dose-dependent weight reductions: 7.3% for 1.2 mg, 9.4% for 1.8 mg, and 10.7% for 2.4 mg, compared to 1.0% in the placebo group.
The MOMENTUM trial enrolled 391 participants with overweight or obesity, excluding those with type 2 diabetes, who had a mean age of 50 years and a mean BMI of 37 kg/m² at baseline. Participants were randomly assigned to receive pemvidutide doses of 1.2 mg, 1.8 mg, 2.4 mg, or placebo over 48 weeks, with dose titration for the 2.4 mg group.
At the end of 48 weeks, pemvidutide demonstrated mean weight reductions of 10.3% for 1.2 mg, 11.2% for 1.8 mg, and 15.6% for 2.4 mg, compared to 2.2% in the placebo group. Notably, 20% or greater weight loss was achieved by 2.0% (placebo), 10.0% (1.2 mg), 9.5% (1.8 mg), and 32.1% (2.4 mg) of participants.
Moreover, pemvidutide was associated with significant reductions in triglyceride levels across all doses: -21.7% for 1.2 mg, -22.3% for 1.8 mg, and -34.9% for 2.4 mg, contrasting with a 7.3% increase in the placebo group.
Dr. Aronne also presented MRI-based body composition analyses, revealing that pemvidutide users experienced a mean loss of 21.9% lean mass, predominantly from fat reduction (78.1%).
“With its promising safety profile and potential to improve conditions like dyslipidemia and hypertension associated with obesity, pemvidutide could offer a valuable long-term treatment option for diverse segments of the obese population,” Dr. Aronne concluded.
The study authors are gearing up for larger Phase 3 trials to validate the safety and clinical effectiveness of pemvidutide for managing weight. Additionally, given that obesity can contribute to excess liver fat accumulation and nonalcoholic steatohepatitis (NASH), they are investigating pemvidutide’s potential benefits in patients with these conditions.
Reference:
Aronne LJ, Harris MS, Roberts MS, et al. Pemvidutide, a GLP-1/Glucagon Dual Receptor Agonist, in Subjects with Overweight or Obesity—A 48-Week, Placebo-Controlled, Phase 2 (MOMENTUM) Trial. Presented at: American Diabetes Association (ADA) 84th Scientific Sessions. June 21 – 24, 2024. Orlando, FL.

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