Clinical outcomes of SGLT2 inhibitors among patients with MASLD and T2DM

Sep 26, 2025Diabetes research and clinical practice

Health results of SGLT2 inhibitor treatment in patients with fatty liver disease and type 2 diabetes

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Abstract

SGLT2 inhibitors are associated with a 65% lower risk of major clinical events in patients with MASLD and type 2 diabetes compared to DPP4 inhibitors.

This study included 10,232 patients with MASLD and type 2 diabetes initiating either SGLT2 inhibitors or DPP4 inhibitors.
The primary outcome assessed was a combination of all-cause mortality, major adverse cardiovascular events, kidney events, and liver outcomes.
SGLT2 inhibitors showed a significant association with reduced risks for the composite outcome as well as for each individual component.
Results from subgroup and sensitivity analyses were consistent with the main findings.

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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.

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Clinical outcomes of SGLT2 inhibitors among patients with MASLD and T2DM

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