Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexists with type 2 diabetes mellitus (T2DM), increasing the risk of cardiovascular, renal, and hepatic complications. Pharmacologic options remain limited. This study aimed to evaluate the association between sodium-glucose cotransporter-2 inhibitors (SGLT2is) and one-year clinical outcomes in patients with MASLD and T2DM, compared to dipeptidyl peptidase-4 inhibitors (DPP4is).
Approach and results: This retrospective cohort study used data from 147 healthcare organizations in the TriNetX global research network. Adults with MASLD and T2DM initiating SGLT2is or DPP4is between January 1, 2013, and February 28, 2025, were identified. After matching, 10,232 patients were included in each group. The primary outcome was a composite of all-cause mortality, major adverse cardiovascular events (MACE), kidney events (MAKE), and liver outcomes (MALO). SGLT2is were associated with lower risks of the composite outcome (HR, 0.65) and all individual components. Subgroup and sensitivity analyses yielded consistent results.
Conclusions: Among patients with MASLD and T2DM, SGLT2is were associated with lower risks of major clinical events compared to DPP4is, supporting their potential therapeutic role pending confirmation in randomized trials.
Keywords: DPP4is; MASLD; SGLT2is; T2DM.
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