Efficacy and safety of pemvidutide in metabolic dysfunction-associated steatohepatitis: a GRADE-assessed meta-analysis of randomized controlled trials.

Metabolic dysfunction-associated steatohepatitis (MASH) contributes substantially to liver and cardiometabolic disease. Pemvidutide, a dual GLP-1/glucagon receptor agonist, may provide combined hepatic and systemic benefits. We conducted a meta-analysis of randomized controlled trials comparing pemvidutide versus placebo in adults with MASLD/MASH. Data were pooled using random-effects models to estimate mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). At 12 weeks, pemvidutide significantly reduced liver fat content (MD - 52.90, 95% CI - 71.60 to - 34.20, P < 0.00001), CAP score (MD - 38.30, 95% CI - 70.69 to - 5.91, P = 0.02), body weight (MD - 3.50, 95% CI - 5.00 to - 2.00, P < 0.00001), and blood pressure. At 24 weeks, improvements were seen in ALT (MD - 18.09, 95% CI - 30.12 to - 6.06, P = 0.003), AST (MD - 13.02, 95% CI - 21.84 to - 4.20, P = 0.004), LFC (MD - 45.51, 95% CI - 52.70 to - 38.33, P < 0.00001), and ELF score (MD - 0.44, 95% CI - 0.77 to - 0.11, P = 0.01). Safety was comparable to placebo except for higher mild-to-moderate nausea (P > 0.05). Pemvidutide significantly improves hepatic and metabolic parameters in MASLD/MASH with acceptable tolerability. Larger, longer trials are warranted to confirm antifibrotic efficacy.