Glucagon-Like Peptide-1 Receptor Agonists and Incident Major Adverse Liver Outcomes in People With Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease

Abstract

Aims: Treatment options for metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. While glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve cardiovascular outcomes, comparative effectiveness on liver-related outcomes remains unclear. This study compared the effectiveness of GLP-1 RAs versus SGLT-2 inhibitors on major adverse liver outcomes (MALO), liver cirrhosis and all-cause mortality in people with MASLD and type 2 diabetes. Materials and Methods: This active comparator, new-user cohort study used claims data from Germany (2005–2024), including 45 256 people with MASLD and type 2 diabetes. New users of GLP-1 RAs (n = 9993) and SGLT-2 inhibitors (n = 35 263) were weighted using matching weights. The primary outcome was MALO, while secondary outcomes comprised individual MALO components (decompensation events, liver transplantation, hepatocellular carcinoma (HCC)), liver cirrhosis and all-cause mortality. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated with weighted Cox proportional hazard models. Results: Over a median 4.3-year follow-up, new users of GLP-1 RAs had a lower hazard of MALO (HR 0.91, 95% CI 0.78–1.07). This association appeared stronger using an on-treatment approach (HR 0.78, 95% CI 0.58–1.03) and when restricting to hospital diagnoses in primary position (HR 0.77, 95% CI 0.56–1.07). Benefits were also observed for liver cirrhosis (HR 0.88), decompensation events (HR 0.91), HCC (HR 0.76), but not all-cause mortality (HR 1.04). Conclusions: GLP-1 RAs were associated with a potentially lower hazard for incident MALO and liver cirrhosis compared with SGLT-2 inhibitors in people with MASLD and type 2 diabetes, suggesting a possible therapeutic advantage for liver-specific outcomes in this population.