Glucagon-Like Peptide-1 Receptor Agonists and Hepatic Decompensation Events in Patients With Cirrhosis and Diabetes

Abstract

The study sought to compare the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas, or sodium-glucose cotransporter-2 (SGLT-2) inhibitors in reducing decompensation events, among patients with cirrhosis and type 2 diabetes. This population-based, retrospective cohort study included patients with type 2 diabetes and cirrhosis, in a commercial healthcare database (IBM MarketScan). We constructed 3 pairwise, 1:1 propensity score (PS)-matched cohorts of adults initiating GLP-1RAs or a comparator medication (ie, DPP-4 inhibitors [2006-2020], sulfonylurea [2005-2020], or SGLT-2 inhibitors [2013-2020]). Patients were followed in an as-treated approach for decompensation events (ie, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, or esophageal variceal hemorrhage). Within each PS-matched cohort, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs), controlling for >90 baseline characteristics. Over 132 days of median follow-up (interquartile range, 73-290 days), PS-matched rates of any decompensation were significantly lower among GLP-1RA initiators, versus DPP-4 inhibitor initiators (105.2 vs 144.0 per 1000 person-years [PY]; HR, 0.68; 95% CI, 0.53-0.88; n= 1431 pairs), and versus sulfonylureas (97.3 vs 144.0 per 1000 PY; HR, 0.64; 95% CI, 0.48-0.84; n= 1246 pairs). Similar, inverse associations were found for individual decompensation events, including ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome (HR, 0.66; 95% CI, 0.45-0.97; and HR, 0.66; 95% CI, 0.46-0.94, respectively); esophageal variceal hemorrhage (HR, 0.62 [95% CI, 0.41-0.92; and HR, 0.59; 95% CI, 0.37-0.92, respectively); and hepatic encephalopathy (HR, 0.76; 95% CI, 0.55-1.06; and HR, 0.60; 95% CI, 0.39-0.92, respectively). Results persisted in subgroups of patients with and without previously decompensated cirrhosis. In contrast, decompensation rates were similar when GLP-1RAs and SGLT-2 inhibitors were directly compared (103.5 vs 112.8 per 1000 PY; HR, 0.89; 95% CI, 0.62-1.28). Among cirrhotic patients with type 2 diabetes, we find high rates of decompensation, consistent with previous reports; these rates were substantially lower among GLP-1RA initiators compared with DPP-4 inhibitors or sulfonylureas.