Reduced mortality and morbidity associated with metformin and SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus and cirrhosis.

INTRODUCTION: Evidence for dual antidiabetic therapy in type 2 diabetes mellitus patients with cirrhosis is limited. This study compared 5-year mortality, composite hepatic decompensation risk, and hepatocellular carcinoma occurrence in patients with diabetes and cirrhosis who were either on metformin monotherapy or on dual metformin and sodium-glucose co-transporter-2 inhibitor (SGLT2-I) therapy.

METHODS: This retrospective study used the TriNetX Research Network to identify propensity score-matched patients treated with either metformin or dual metformin and SGLT2-I therapy. Our outcomes were all-cause mortality, a composite of hepatic decompensation events, and hepatocellular carcinoma (HCC) occurrence over 5 years. We estimated hazard ratios within each cohort with 95% confidence intervals (CI) and Kaplan-Meier estimates for time-to-event distributions with Log-rank tests. We were able to stratify our cohorts by age, sex, race, and ethnicity. We further investigated a subset of diabetic patients with cirrhosis due to MASH.

RESULTS: In our propensity score-matched cohorts of type 2 diabetes patients with cirrhosis, those on dual metformin and SGLT2-I therapy had decreased risk for mortality (HR 0.57, 95%CI 0.41-0.81), reduced composite risk of becoming decompensated (HR 0.63, 95%CI 0.43-0.93) and less than half the risk for developing HCC (HR 0.43, 95%CI 0.21-0.88) compared to those on mono metformin therapy. We did not find a difference between mono or dual therapy treatment for mortality, decompensation, or HCC risks in the subset of patients with MASH cirrhosis.

CONCLUSION: Dual metformin and SGLT2-I treatment in type 2 diabetes patients with cirrhosis are associated with improved mortality and hepatic complications.