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 inhibitors (SGLT-2i), 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 7,867 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-2i 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-2i 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-2i was observed from 2010-2017 to 2017-2023, with pioglitazone and SGLT-2i being prescribed more frequently in Asian countries than in Western countries (pioglitazone:17.9% vs. 3.8%, SGLT-2i: 34.4% vs.7.3%; P<0.001). After propensity score matching, in competing risk models, SGLT-2i use was significantly associated with a lower risk of developing both LREs (SHR: 0.23, 95%CI 0.08-0.69, P=0.009) and liver stiffness progression (HR: 0.54, 95%CI 0.35-0.86, P=0.008) 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.