Similar weight loss with semaglutide regardless of diabetes and cardiometabolic risk parameters in individuals with metabolic dysfunction‐associated steatotic liver disease: Post hoc analysis of three randomised controlled trials

Aims: Weight loss mediated by glucagon‐like peptide‐1 (GLP‐1) analogues is lower in patients with type 2 diabetes versus those without. Type 2 diabetes and obesity are risk factors for metabolic dysfunction‐associated steatotic liver disease (MASLD) and associated steatohepatitis (MASH). We evaluated weight changes in adults with MASLD/MASH with or without type 2 diabetes receiving the GLP‐1 analogue semaglutide.

Materials and Methods: This was a post hoc analysis of data from three 48–72‐week randomised trials investigating the effect of semaglutide versus placebo in adults with MASLD (NCT03357380) or biopsy‐confirmed MASH (NCT02970942 and NCT03987451). Pooled data for semaglutide (0.4 mg once daily and 2.4 mg once weekly [n = 163]) and placebo (n = 137) were analysed at 1 year. Weight changes were analysed by type 2 diabetes status (type 2 diabetes [n = 209], pre‐type 2 diabetes [n = 51] and no diabetes [n = 40]) and by other cardiometabolic risk parameters using analysis of covariance and Spearman's rank correlations.

Results: The overall mean weight change was −11.1 kg (−11.7%) and −0.7 kg (−0.6%) with semaglutide and placebo, respectively. While numerically higher for people without type 2 diabetes, estimated treatment differences with semaglutide versus placebo were similar overall for people with type 2 diabetes (−10.2 kg; −10.8%), pre‐type 2 diabetes (−9.8 kg; −10.2%) and no diabetes (−11.6 kg; −13.1%). Differences between groups were not statistically significant (p > 0.50 for all). Baseline fasting plasma glucose, glycated haemoglobin, insulin levels, insulin resistance and lipids did not correlate with weight change.

Conclusions: People with MASLD/MASH had similar semaglutide‐mediated weight loss regardless of type 2 diabetes status and other cardiometabolic risk parameters.