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

Abstract

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.

Keywords Cirrhosis, type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonists, hepatocellular carcinoma, nonalcoholic steatohepatitis

Ann Gastroenterol 2023; 36 (5): 555-563