Original Abstract

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease is common among individuals with type 2 diabetes mellitus and substantially increases the risk of liver cirrhosis and hepatocellular carcinoma. Effective therapies that improve metabolic control while preventing advanced liver outcomes are limited. AIMS: To evaluate the association between semaglutide treatment and the risk of liver cirrhosis and hepatocellular carcinoma in adults with type 2 diabetes mellitus. METHODS: We performed a retrospective population-based cohort study using electronic health records from a large integrated healthcare organization. Adults with type 2 diabetes mellitus and no prior diagnosis of liver cirrhosis or hepatocellular carcinoma were included. Exposure was defined as treatment with semaglutide for at least four consecutive months compared with matched control patients. Cox proportional hazards models estimated adjusted hazard ratios with 95% confidence intervals, accounting for demographic factors, body mass index, smoking status, glycaemic control, other antidiabetic treatments and baseline liver fibrosis risk. RESULTS: Among 71 612 individuals, 35 806 received semaglutide and 35 806 were matched controls. Over a median follow-up of 4628 days for liver cirrhosis and 4090 days for HCC, 245 patients developed liver cirrhosis and 21 developed hepatocellular carcinomas. In the Cox model, there was no association between semaglutide treatment and the diagnosis of liver cirrhosis (HR 1.3, 95% CI 0.98-1.77) or hepatocellular carcinoma (HR 0.6, 95% CI 0.21-1.51). CONCLUSIONS: In this real-world study, semaglutide treatment was not associated with a reduced risk of liver cirrhosis or hepatocellular carcinoma among adults with type 2 diabetes mellitus.