Comparative effectiveness of GLP ‐1 receptor agonists, SGLT2 inhibitors and DPP ‐4 inhibitors on liver outcomes in metabolic dysfunction‐associated steatotic liver disease: A retrospective cohort study

AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in individuals with type 2 diabetes mellitus (T2DM). MASLD carries a substantial risk of progression to cirrhosis or hepatocellular carcinoma (HCC). Whether the metabolic benefits of antidiabetic therapy may alter this progression remains under-investigated. We aimed to evaluate the incidence of cirrhosis or HCC across the commonly used second-line antidiabetic agent classes in patients with coexisting MASLD and T2DM. MATERIALS AND METHODS: We conducted a retrospective cohort study using healthcare claims databases in the United States. Patients with MASLD and T2DM initiating one of the three antidiabetic agent classes, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) were included. Propensity score (PS) matching was applied to control for baseline differences between treatment groups. Cumulative incidence of cirrhosis or HCC over 2 years was estimated with Kaplan-Meier method, and risks between treatment groups were compared using Cox regression. RESULTS: The analysis included three PS-matched cohorts: 4538 GLP-1RA versus DPP-4i pairs, 4754 SGLT2i versus GLP-1RA pairs, and 4333 SGLT2i versus DPP-4i pairs. In the intention-to-treat analysis, no statistically significant differences in the risk of cirrhosis or HCC were observed at 2 years across treatment comparisons (GLP-1RA vs. DPP-4i: hazard ratios [HR] 0.80, 95% confidence intervals [CI] 0.58-1.09; GLP-1RA vs. SGLT2i: HR 0.76, 95% CI 0.55-1.04; SGLT2i vs. DPP-4i: HR 0.78, 95% CI 0.58-1.05). CONCLUSIONS: In this large real-world study, we found no clear or consistent differences in liver-related outcomes across GLP-1RA, SGLT2i, and DPP-4i users over a 2-year period.