Semaglutide improves liver enzymes and fatty liver index in patients with obesity and cardiovascular disease - results from the SELECT trial.

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease is a potential driver of cardiovascular (CV) risk in people with obesity. The SELECT CV outcomes trial showed that treatment with the glucagon- like peptide-1 analog semaglutide resulted in a 20% reduction in the risk of major CV events in patients with overweight or obesity and established atherosclerotic CV disease (ASCVD) but without diabetes. In this analysis, we assessed the effects of semaglutide on liver enzymes and predicted hepatic steatosis in SELECT participants. Method(s): SELECT was a multicenter, randomized, double-blind, placebo-controlled, event-driven trial that enrolled 17,604 patients aged >=45 years. Patients were randomized (1:1) to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo in addition to standard of care for CV disease prevention. For this analysis, liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT), as well as the fatty liver index (FLI), an algorithm based on body mass index, waist circumference, triglycerides and GGT predictive of hepatic steatosis, were assessed over 104 weeks. Result(s): ALT, AST and GGT declined rapidly after initiation of semaglutide treatment, reaching a nadir at 20 weeks, after which ALT and AST increased over time while GGT remained stable. The estimated treatment difference vs placebo at week 104 was -1.9 U/L (95% confidence interval [CI] -2.6, -1.2; p<0.0001), -0.9 U/L (95% CI -1.3, -0.5; p<0.0001) and -8.2 U/L (95% CI -9.5, -6.8; p<0.0001), respectively (Figs. 1a-c). A 6% (95% CI 0.93, 0.95; p<0.0001) greater decrease from baseline with semaglutide vs placebo was observed for ALT, 3% (95% CI 0.96, 0.98; p <0.0001) for AST and 17% (95% CI 0.82, 0.84; p <0.0001) for GGT. In line, FLI decreased by 16.1 (95% CI -16.7, -15.6; p<0.0001) upon semaglutide treatment vs placebo (Fig. 1d), corresponding to a 28% greater decrease in FLI (95% CI 0.71, 0.73; p<0.0001). Semaglutide treatment also resulted in a -9.39% mean change in body weight over 104 weeks vs -0.88% with placebo. Conclusion(s): Semaglutide treatment resulted in a significant and rapid improvement in liver enzymes and FLI, suggesting a beneficial effect on liver health in patients with established ASCVD but without diabetes. These results are consistent with the weight loss induced by semaglutide, as excess body fat is a major risk factor for liver steatosis and inflammation.