Association of GLP1-Receptor Agonists with Risk of Hepatocellular Carcinoma: A Retrospective Cohort Study

Jun 30, 2025Drug safety

Use of GLP-1 Receptor Drugs and Risk of Liver Cancer: A Look Back Study

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Hepatocellular carcinoma occurred in 302 (0.30%) GLP-1RA users compared to 230 (0.23%) DPP4i users.

GLP-1 receptor agonist use is associated with a statistically significant increase in the risk of hepatocellular carcinoma compared to dipeptidyl peptidase-4 inhibitor use.
The odds ratio for developing hepatocellular carcinoma in GLP-1RA users is 1.31, indicating a 31% higher risk compared to DPP4i users.
An increased risk of hepatocellular carcinoma is observed with GLP-1RA use for more than 6 months, while use for less than 6 months shows a similar risk to DPP4i.
The findings suggest that while the risk is modest, further investigation is necessary due to the rising use of GLP-1RA and their expanding applications.

AI simplified

BACKGROUND: The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has exponentially increased owing to their favorable cardio-renal-metabolic effects. Some studies have raised concerns about a potential association between GLP-1RA use and malignancy. This study aimed to examine the association between GLP-1RA use and risk of hepatocellular carcinoma (HCC).

METHODS: This retrospective propensity score (PS)-matched cohort study used data from the Veterans Health Administration (years 2006-2021). Using a new-user active comparator design, the study included adults who initiated a GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP4i) as an active comparator and had no prior history of HCC or liver transplantation. The primary outcome was incident HCC. We developed a PS that included 133 variables encompassing diabetes severity, hepatic conditions, liver disease scores, vital signs, laboratory investigations, comorbidity scores, and use of other medication classes.

RESULTS: Of 147,969 GLP-1RA and 263,664 DPP4i users, 100,248 pairs of GLP-1RA and DPP4i users were PS-matched. Hepatocellular carcinoma occurred in 302 (0.30%) GLP-1RA users and in 230 (0.23%) DPP4i users (odds ratio [OR]: 1.31, 95% confidence interval [95% CI]: 1.11-1.56). Secondary analysis, which stratified patients by duration of medication use, showed an increased risk of HCC in association with GLP-1RA use > 6 months, but similar HCC risk if medication use was < 6 months (OR: 0.96; 95% CI 0.68-1.35).

CONCLUSIONS: Glucagon-like peptide-1 receptor agonists use was associated with a modest but statistically significant increase in HCC risk versus DPP4i use. Although the reported benefits of GLP-1RA seem to far exceed this modest increased risk, further studies are warranted due to exponentially increasing GLP-1RA use and their broadening indications.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗

Association of GLP1-Receptor Agonists with Risk of Hepatocellular Carcinoma: A Retrospective Cohort Study

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief