The overall mean weight change was -11.1 kg (-11.7%) with in adults with /MASH.
Weight loss with semaglutide was significantly greater than with placebo, which resulted in a mean weight change of -0.7 kg (-0.6%).
Individuals without type 2 diabetes experienced a numerically higher weight loss with semaglutide compared to those with type 2 diabetes or pre-type 2 diabetes.
Estimated treatment differences for weight loss with semaglutide compared to placebo were similar across groups: type 2 diabetes (-10.2 kg), pre-type 2 diabetes (-9.8 kg), and no diabetes (-11.6 kg).
No statistically significant differences in weight loss were observed between the diabetes status groups (p > 0.50 for all).
Baseline metabolic parameters, including fasting plasma glucose and insulin levels, did not correlate with weight change.
Simplified
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 (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 .
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.
Key numbers
-11.1 kg
Mean Weight Change with
Weight change at 1 year for group.
-0.7 kg
Mean Weight Change with Placebo
Weight change at 1 year for placebo group.
209 of 300
Participants with Type 2 Diabetes
Total participants with type 2 diabetes in the study.
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MJA: consultancy and sponsored lectures for Norgine and Novo Nordisk. TO: no conflicts of interest to declare. MSP: employee and shareholder of Novo Nordisk. A‐SS: employee and shareholder of Novo Nordisk. MT: employee and shareholder of Novo Nordisk. MR: research grants from Boehringer Ingelheim and Novo Nordisk; consulting or advisory boards for AstraZeneca, Boehringer Ingelheim, Echosens, Eli Lilly, MSD and Novo Nordisk; speaker fees from AstraZeneca, Madrigal, MSD and Novo Nordisk.
