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
Gregor A. Maier, Ramon A. Hofmann, Michael Roden, Wolfgang Rathmann, Oliver KussABSTRACT
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.