GLP-1s associated with lower risk of hepatic decompensation than other diabetes drugs

Patients taking glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes had lower risk of hepatocellular carcinoma than those on insulin or sulfonylureas, and hepatic decompensation risk was reduced compared with five comparison diabetes drug classes, a study found.

Glucagon-like peptide-1 (GLP-1) receptor agonists were associated with a reduced risk of hepatocellular carcinoma (HCC) and hepatic decompensation compared with other medications for type 2 diabetes, a study found.

To evaluate the effects of drugs on HCC risk in a real-world population, researchers conducted a retrospective cohort study among patients with type 2 diabetes who were prescribed GLP-1 receptor agonists or other diabetes medications and had no prior diagnosis of HCC. First-time diagnosis of HCC and hepatic decompensation during five years of follow-up were compared between patients prescribed GLP-1 receptor agonists versus other diabetes drugs. Results were published April 29 by Gastroenterology.

Among 1,890,020 patients with diabetes, GLP-1 receptor agonists were associated with a lower risk of incident HCC compared to insulin (hazard ratio [HR], 0.20; 95% CI, 0.14 to 0.31) and sulfonylureas (HR, 0.39; 95% CI, 0.21 to 0.69). There was no significant difference in risk between GLP-1 receptor agonists and metformin, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, or thiazolidinediones. However, GLP-1 receptor agonists were associated with a significantly lower risk of hepatic decompensation compared with all six other classes of diabetes drugs.

The study also found that the reduced risks were seen in patients with and without fatty liver disease, with more profound effects in patients without liver disease, and that similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. They also observed that GLP-1 receptor agonist combination therapies were associated with decreased risk for HCC and hepatic decompensation compared with monotherapies.

Limitations of the study include its retrospective design and limited length of follow-up.

"Given the alarming increase in HCC and its poor prognosis, as well as a significantly increased risk for HCC in patients with [type 2 diabetes], further preclinical and clinical studies are warranted to investigate the underlying mechanisms" for GLP-1 receptor agonists' apparent beneficial effects on the liver, the study authors wrote.