Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity

Summary Background Obesity and type 2 diabetes are drivers of non‐alcoholic fatty liver disease (NAFLD). Glucagon‐like peptide‐1 analogues effectively treat obesity and type 2 diabetes and may offer potential for NAFLD treatment. Aim To evaluate the effect of the glucagon‐like peptide‐1 analogue, semaglutide, on alanine aminotransferase (ALT) and high‐sensitivity C‐reactive protein (hsCRP) in subjects at risk of NAFLD. Methods Data from a 104‐week cardiovascular outcomes trial in type 2 diabetes (semaglutide 0.5 or 1.0 mg/week) and a 52‐week weight management trial (semaglutide 0.05‐0.4 mg/day) were analysed. Treatment ratios vs placebo were estimated for ALT (both trials) and hsCRP (weight management trial only) using a mixed model for repeated measurements, with or without adjustment for change in body weight. Results Elevated baseline ALT (men >30 IU/L; women >19 IU/L) was present in 52% (499/957) of weight management trial subjects. In this group with elevated ALT, end‐of‐treatment ALT reductions were 6%‐21% (P