Glucagon‐Like Peptide‐1 Receptor Agonists and Liver Outcomes in Patients With MASLD and Type 2 Diabetes

ABSTRACT Background and Aims Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) have demonstrated long‐term liver benefits in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) and type 2 diabetes (T2D). However, no direct comparison between these therapies has been conducted. This study aimed to compare major adverse liver outcomes (MALOs) between GLP‐1 RAs and SGLT2is in patients with MASLD and T2D. Methods Using the TriNetX Research Network, a multinational and multi‐institutional database, we identified adults with MASLD and T2D who received their first prescription for either a GLP‐1 RA or an SGLT2i between January 2010 and June 2023. We conducted a propensity score‐matched (PSM) cohort study comparing new users of GLP‐1 RAs and SGLT2is. The primary outcome was the risk of MALOs, a composite endpoint consisting of decompensated cirrhosis events, hepatocellular carcinoma, and liver transplantation. Secondary outcomes included all‐cause mortality and individual components of the primary outcome. Results This study included 15,176 pairs of patients treated with either a GLP‐1 RA or a SGLT2i. The adjusted hazard ratio (HR) for MALO associated with GLP‐1 RAs relative to SGLT2is was 0.84 (95% confidence interval [CI]: 0.73–0.97; incidence rate: 88.9 versus 105.3 events per 10,000 person‐years), primarily driven by reduction in decompensated cirrhosis events (adjusted HR: 0.83, 95% CI: 0.71–0.96). GLP‐1 RAs were associated with lower all‐cause mortality (adjusted HR: 0.84, 95% CI: 0.75–0.94). Conclusion GLP‐1 RAs are associated with better long‐term liver outcomes compared to SGLT2is in patients with MASLD and T2D.