228-OR: Effects of Pemvidutide, a GLP-1/Glucagon Dual Receptor Agonist, on Cardioinflammatory Lipids in Subjects with Obesity or Overweight

• Published in: Diabetes (New York, N.Y.) Vol. 74; no. Supplement_1; p. 1
• Main Authors: SUSCHAK, JOHN J., LUCCA ANDRADE, MAYNARA, GEORGES, BERTRAND, ALONSO, CRISTINA, ROBERTS, M S., SCOTT HARRIS, M., BROWNE, SARAH K.
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 20.06.2025
• Subjects: Agonists; Body weight; Body weight loss; Cardiovascular diseases; Cholesterol; Clinical trials; Comorbidity; Congestive heart failure; Diabetes mellitus; Glucagon; Inflammation; Lipids; Low density lipoprotein; Mass spectroscopy; Metabolomics; Obesity; Overweight; Triglycerides; Weight control
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db25-228-OR

Introduction and Objective: Dysregulated lipid profiles in obesity can promote systemic inflammation and increase cardiovascular risk. We previously reported on the effects of pemvidutide, a dual GLP-1/glucagon receptor agonist, on these profiles in a Phase 1 trial in healthy volunteers. The aim of this study was to extend these observations to a Phase 2 clinical trial of pemvidutide in subjects with obesity or overweight. Methods: Subjects with obesity, or overweight and at least 1 obesity-related comorbidity, but without diabetes were randomized 1:1:1:1 to pemvidutide (1.2, 1.8, 2.4 mg) or placebo administered weekly by the subcutaneous route for 48 weeks (N=391; mean BMI 37.4 kg/m2). Metabolomic profiling was conducted in 254 subjects with paired Baseline and Week 48 plasma samples using mass spectrometry or NMR. Results: Pemvidutide reduced body weight by up to 15.6% and atherogenic lipids including total cholesterol, LDL-C, and triglycerides by up to 15.1%, 11.2%, and 34.9%, respectively. Pemvidutide reduced pro-inflammatory lipidomic signatures, including remnant cholesterol, small LDL-C particles, and multiple classes of pro-inflammatory lipids. Reductions in Glyc-A, a biomarker correlated with heart failure, were also observed (Table 1). Conclusion: Pemvidutide elicited significant weight loss and decreases in atherogenic pro-inflammatory lipid species in subjects with obesity or overweight.