Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes

May 1, 2024Gastroenterology

Links Between Diabetes Drugs That Activate GLP-1 Receptors and Liver Cancer or Liver Failure in Type 2 Diabetes Patients

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Abstract

GLP-1 receptor agonists (GLP-1RAs) were associated with a lower risk of incident hepatocellular carcinoma (HCC) in a cohort of 1,890,020 patients with type 2 diabetes mellitus.

The hazard ratio for incident HCC was 0.20 when compared to insulin, indicating a significant reduction in risk.
GLP-1RAs also showed a lower risk of incident HCC with hazard ratios of 0.39 and 0.63 when compared to sulfonylureas and metformin, respectively.
Patients prescribed GLP-1RAs experienced a significantly lower risk of hepatic decompensation compared to six other anti-diabetes medications.
Reduced risks of incident HCC were noted in patients both with and without fatty liver diseases, with more pronounced effects in those without liver diseases.
Similar protective effects of GLP-1RAs were observed in patients regardless of obesity status or the presence of alcohol or tobacco use disorders.

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BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70% of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population.

METHODS: This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC and hepatic decompensating events during a 5-year follow-up was compared between cohorts of patients prescribed GLP-1 RAs vs other anti-diabetes medications. Time-to-first-event analysis was performed using Kaplan-Meier survival analysis with hazard ratio and 95% confidence interval calculated.

RESULTS: GLP-1RAs were associated with a lower risk of incident HCC with hazard ratio of 0.20 [0.14-0.31], 0.39 [0.21-0.69], 0.63 [0.26-1.50] compared with insulin, sulfonylureas, and metformin, respectively. GLP-1RAs were associated with a significantly lower risk of hepatic decompensation compared with 6 other anti-diabetes medications. Reduced risks were observed in patients without and with different stages of fatty liver diseases, with more profound effects in patients without liver diseases. Similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. GLP-1RA combination therapies were associated with decreased risk for HCC and hepatic decompensations compared with monotherapies.

CONCLUSIONS: GLP-1RAs were associated with a reduced risk of incident HCC and hepatic decompensation compared with other anti-diabetes medications in patients with T2DM. These findings provide supporting evidence for future studies to investigate the underlying mechanisms and their clinical use.

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Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes

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