Effect of Antidiabetic Drug Classes on the Risk of Liver-Related Events in Individuals With T2D and MASLD

Background: We investigated the use of type 2 diabetes (T2D) medications, including pioglitazone, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, in individuals with T2D and metabolic dysfunction–associated steatotic liver disease (MASLD), and explored the effect of these medications on long-term risk of liver-related events (LREs) and progression of liver stiffness in a retrospective cohort study. Methods: We enrolled 7867 individuals with T2D and MASLD from 16 tertiary referral centers between February 2004 and January 2023. We recorded the use of pioglitazone, GLP-1RAs, and SGLT-2 inhibitors and analyzed the effects of these antihyperglycemic medications on the risk of developing incident LREs and the progression of liver stiffness over a median of 5.1 years of follow-up. Results: Pioglitazone, GLP-1RAs and SGLT-2 inhibitors were prescribed to 1238 (15.7%), 863 (11.0%), and 2386 (30.3%) individuals with T2D and MASLD, respectively. A significant increase in the utilization of GLP-1RAs and SGLT-2 inhibitors was observed from 2010–2017 to 2017–2023, with pioglitazone and SGLT-2 inhibitors being prescribed more frequently in Asian countries than in Western countries (pioglitazone: 17.9% vs 3.8%; SGLT-2 inhibitors: 34.4% vs 7.3%; P < .001). After propensity score matching, in competing risk models, SGLT-2 inhibitor use was significantly associated with a lower risk of developing both LREs (subdistribution hazard ratio, 0.23; 95% confidence interval, 0.08–0.69, P = .009) and liver stiffness progression (hazard ratio, 0.54; 95% confidence interval, 0.35–0.86, P = .008) after adjusting for potential confounders. Conclusions: SGLT-2 inhibitor use is more prevalent among Asian than Western individuals. SGLT-2 inhibitors are associated with a lower risk of LREs in individuals with T2D and MASLD.