Efficacy and Safety of Pemvidutide in Patients with Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Dose-Specific Meta-Analysis of Randomized Controlled Trials

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is a prevalent and progressive liver disease with limited pharmacologic treatment options. Pemvidutide, a GLP-1-glucagon dual receptor agonist, has shown promise in targeting both hepatic steatosis and fibrosis. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of pemvidutide in adults with MASH. MethodsWe systematically searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL through December 15, 2025, for randomized controlled trials (RCTs) comparing once-weekly subcutaneous pemvidutide (1.2 mg, 1.8 mg, or 2.4 mg) with placebo in adult MASH patients. Primary outcomes were changes in liver fat content (LFC, % via MRI-PDFF) and Enhanced Liver Fibrosis (ELF) score. Secondary outcomes included body weight, glycemic and lipid parameters, blood pressure, heart rate, and adverse gastrointestinal events. Dose-specific pairwise meta-analyses were performed using a random-effects model. ResultsThree RCTs encompassing 370 participants (195 pemvidutide, 175 placebo) were included. Pemvidutide significantly reduced LFC at all doses, with the greatest effect at 1.8 mg (MD = -21.63%, 95% CI: -27.23 to -16.02; p<0.0001). ELF score improvement was significant at 1.2 mg and 1.8 mg doses but not at 2.4 mg. Across all doses, body weight decreased significantly, while HbA1c remained unchanged. Pemvidutide also reduced systolic blood pressure and total cholesterol (1.8 mg and 2.4 mg), with modest HDL reduction at 2.4 mg. Mild-to-moderate gastrointestinal adverse events were observed, with nausea more frequent at 1.8 mg. ConclusionsPemvidutide is effective in reducing liver fat and improving cardiometabolic parameters in MASH, with a favorable safety profile. Dose-specific effects on fibrosis suggest potential early antifibrotic activity, highlighting its promise as a dual-targeted therapy for MASH. Further long-term studies are warranted to confirm sustained hepatic and metabolic benefits.