Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study

• DOI: 10.1016/j.jhep.2024.07.006
• Publication Date: 2024-07-11T21:27:51Z
• Authors: Stephen A. Harrison; Sarah K. Browne; John J. Suschak; Shaheen Tomah; Julio A. Gutierrez; Jay Yang; M. Scot Roberts; M. Scott Harris
• Keywords: Placebo-controlled study

Background & AimsThis was a randomized, double-blind, placebo-controlled study to assess the effects of pemvidutide, glucagon-like peptide-1 (GLP-1)/glucagon dual receptor agonist, on liver fat content (LFC) in subjects with metabolic dysfunction-associated steatotic disease (MASLD).MethodsSubjects BMI ≥28.0 kg/m2 and LFC ≥10% by magnetic resonance imaging-proton density fraction were randomized 1:1:1:1 pemvidutide at 1.2 mg, 1.8 or 2.4 placebo administered subcutaneously once weekly for 12 weeks. Participants stratified according diagnosis type 2 diabetes mellitus (T2DM). The primary efficacy endpoint relative reduction (%) from baseline after weeks treatment.Results94 dosed. Median across population 36.2 20.6%; 29% had T2DM. At Week 12, reductions (1.2 mg) 46.6% [95% CI -63.7 -29.6], (1.8 68.5% -84.4 -52.5], (2.4 57.1% -76.1 -38.1] versus 4.4% -20.2 11.3] (p <0.001 vs. placebo, all treatment groups), 94.4% 72.2% achieving 30% 50% 55.6% normalization (≤5% LFC) mg dose. Maximal responses weight loss (-4.3%; p <0.001), alanine aminotransferase (-13.8 IU/L; = 0.029), corrected cT1 (-75.9 ms; 0.002) observed Pemvidutide well-tolerated doses no severe serious adverse events.ConclusionsIn MASLD, yielded significant LFC, markers hepatic inflammation, body compared placebo.Impact implicationsMASLD, MASH, are strongly associated overweight obesity it is believed that excess an important driver these diseases. Glucagon-like (GLP-1R) agonists elicit through centrally peripherally mediated appetite. Unlike GLP-1R agonists, glucagon (GCGR) act directly stimulate fatty acid oxidation inhibit lipogenesis, potentially providing more potent mechanism than alone. This demonstrated ability once-weekly GLP-1R/GCGR significantly reduce inflammatory activity, weight, suggesting may be effective both MASH obesity.Clinical Trial NumberNCT05006885.