GLP-1 receptor agonists and adverse outcomes in patients with type 2 diabetes and chronic viral hepatitis

Background/Aims: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a novel class of anti-diabetic drugs that can treat obesity and type 2 diabetes (T2D). T2D and chronic viral hepatitis (CVH) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate the effect of GLP-1RA on liver and non-liver complications among patients with T2D and CVH in the United States. Methods: Patients with T2D and CVH initiating GLP-1RA were included (2013-2022) in Merative™ Marketscan® Research Databases. Primary outcomes included (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Cox proportional hazards models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 9,499 patients with T2D and CVH were included after 1:4 propensity score matching. Compared with non-GLP-1RA (N=7,366), GLP-1RA use (N=2,133) was associated with significantly lower risks of any liver-related outcomes (HR 0.71, 95% CI 0.57-0.87; P=0.001), HCC (HR 0.53, 95% CI 0.31-0.93; P=0.028), cirrhosis (HR 0.70, 95% CI 0.56-0.86; P<0.001), CKD (HR 0.67, 95% CI 0.53-0.84; P<0.001). A trend toward a lower risk of CVD (HR 0.82, 95% CI 0.66-1.03; P=0.089) and non-liver cancer (HR 0.73, 95% CI 0.53-1.01; P=0.055) was observed among GLP-1RA users, although the association did not reach statistical significance. Conclusions: GLP-1RA use was associated with lower risks of cirrhosis, HCC, and CKD among patients with T2D and CVH, with nonsignificant trends toward lower risks of CVD and non-liver cancer.