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

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.