SGLT2 inhibitors and cardiovascular outcomes in metabolic dysfunction-associated steatotic liver disease: A real-world retrospective cohort study

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health issue associated with increased cardiovascular risk. SGLT2 inhibitors offer cardioprotective benefits and may improve MASLD-related outcomes. We aimed to investigate the association between SGLT2 inhibitors use and cardio-hepatic events in patients with MASLD.

We conducted a retrospective cohort study using the TriNetX Network, including 1,280,057 adults (≥18 years) with MASLD without prior alcohol-associated liver disease between 2014 and 2022. Patients were stratified by SGLT2 inhibitors use. Propensity score matching (1:1, PSM) was performed to balance baseline characteristics between two cohorts. Hazard ratio (HR) with 95% confidence intervals (CIs) were calculated using Cox proportional hazard models.

After PSM, there were 69,970 patients with MASLD per each cohort. Mean follow-up was 3.70±2.08 and 4.14±2.66 years for SGLT2 inhibitor users and non-users, respectively. SGLT2 inhibitor use was associated with lower all-cause mortality (HR 0.600 [95% CI, 0.580-0.621]) and hospitalization (HR 0.788 [0.777-0.800]). Cardiovascular benefits included reduced risks of acute heart failure exacerbation (HR 0.872 [0.849-0.896]), acute myocardial infarction (HR 0.916 [0.882-0.952]), cerebral infarction (HR 0.954 [0.916-0.994]), and cardiac arrest (HR 0.661 [0.609-0.718]). Hepatic outcomes showed lower risks of acute liver failure (HR 0.704 [0.643-0.770]) and cirrhosis (HR 0.898 [0.861-0.936]). Safety analysis revealed a lower incidence of acute kidney injury (HR 0.797 [0.779-0.816]) without significant difference for hypoglycemia (HR 0.963 [0.914-1.014]).

SGLT2 inhibitors in MASLD patients were associated with reduced mortality, hospitalization, cardiovascular events, and liver complications, highlighting potential benefits beyond glycemic control.