Dual metformin and glucagon-like peptide-1 receptor agonist therapy reduces mortality and hepatic complications in cirrhotic patients with diabetes mellitus

BACKGROUND: Type 2 diabetes (T2DM) can accelerate the progression of cirrhosis. The potential for oral diabetes medications to counteract the mortality and morbidity of chronic liver diseases is unclear. METHODS: We compared the effectiveness of dual metformin and glucagon-like peptide-1 receptor agonists (GLP1-RA) vs. metformin treatment alone in reducing mortality and hepatic complications in cirrhotic patients with T2DM. We evaluated propensity score-matched cohorts of T2DM and cirrhosis patients treated with metformin or dual metformin and GLP1-RA therapy. Data were obtained from the TriNetX Research Network. Our outcomes were all-cause mortality, composite risk of hepatic decompensation, and hepatocellular carcinoma (HCC). RESULTS: Compared to patients on metformin alone, dual metformin and GLP1-RA therapy users had a lower risk for both death (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.42-0.89; P=0.011) and hepatic decompensation (HR 0.65, 95%CI 0.46-0.93; P=0.02) over 5 years. Patients on dual therapy had a lower risk for HCC (HR 0.44, 95%CI 0.26-0.74; P=0.001) compared to mono-metformin therapy patients. CONCLUSION: In our multicenter retrospective study, dual therapy was associated with better mortality and morbidity in cirrhosis patients with T2DM compared to those on metformin alone.