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Abstract Background and Aims Semaglutide has been studied in patients with metabolic dysfunction‐associated steatohepatitis (MASH) due to potential benefit from weight loss on liver inflammation. However, preclinical studies suggest that MASH improvement may be independent of weight loss. We aim to assess the impact of semaglutide on MASH in relation to weight loss. Methods This retrospective study included 420 patients with diabetes on semaglutide for at least 12 months between 2011 and 2022. Exclusion criteria were liver disease other than MASH, decompensated cirrhosis, malignancy, and bariatric surgery. Primary endpoints were clinically significant improvements in AST or ALT (mean difference > 6.3 U/L and > 10.6 U/L respectively). Statistical analysis included Student's t‐test/ANOVA, Wilcoxon signed‐rank test/Friedman test as appropriate, and binary logistic regression. Results Median duration of semaglutide was 22.5 months and 80% of patients received 1 mg/week. BMI improved by a mean (SD) of 1.9 points (2.8), weight by 13.3 lbs. (19.1), AST by 4.1 U/L (11.5), and ALT by 5.3 U/L (14.2). In 28% and 22% of patients respectively, AST and ALT had a clinically significant improvement. MASH scores (NFS, FIB4, APRI) improved after semaglutide (p