Meta-Analysis Finds No Link Between GLP-1 Drugs and Bile Duct Cancer Risk in Diabetes Patients

What the researchers found

Across four observational studies (three cohort, one case-control):

- GLP-1 receptor agonists: pooled HR 1.07 (95% CI: 0.70–1.63) — no significant association with cholangiocarcinoma

- DPP-4 inhibitors: pooled HR 1.05 (95% CI: 0.83–1.34) — no significant association

- Pooled risk ratio analyses yielded similarly non-significant results for both drug classes

- All included studies were assessed as having low risk of bias per the Newcastle-Ottawa Scale

- Findings provide reassurance about the safety of incretin-based therapies regarding bile duct cancer risk

Why it matters

With millions of people now taking GLP-1 drugs for diabetes and obesity, understanding their cancer risk profile is critical. Cholangiocarcinoma is a rare but aggressive cancer, and even a small increase in risk would affect many people at population level. This meta-analysis provides early reassurance that incretin-based therapies don't appear to increase this particular cancer risk.

How the study worked

Systematic review and meta-analysis following PRISMA 2020 guidelines, registered in PROSPERO. Databases searched included PubMed, ProQuest, EBSCOhost, Wiley, and SAGE. Four eligible observational studies were included. Study quality was assessed using the Newcastle-Ottawa Scale. Pooled hazard ratios and risk ratios with 95% CIs were calculated using a random-effects model.

What this study cannot tell us

Only four observational studies were available, limiting statistical power. Observational studies cannot establish causation. The relatively rare incidence of cholangiocarcinoma means even pooled data may be insufficient to detect small risk increases. Follow-up periods may have been too short to capture cancers with long latency periods. The analysis didn't distinguish between different GLP-1 RAs or DPP-4 inhibitors.

How to read the evidence

This is a systematic review and meta-analysis of observational studies — the best available evidence for this safety question. However, only four studies were included, all observational, limiting the certainty of conclusions compared to what a meta-analysis of RCTs would provide.

When this study was published

Published in 2025, this is very current safety evidence addressing concerns about incretin-based therapies and cancer risk.

The bigger picture

Safety concerns about GLP-1 drugs and cancer have been a persistent topic since these medications were first introduced. While some early signals suggested possible associations with thyroid and pancreatic cancers, most large-scale analyses have been reassuring. This study adds bile duct cancer to the list of cancers that don't appear to be increased by incretin-based therapies, though ongoing pharmacovigilance remains important.

Questions still open

• Would longer follow-up periods reveal a delayed association between incretin therapies and cholangiocarcinoma?
• Are there specific GLP-1 receptor agonists that might carry different cancer risk profiles?
• Do the reassuring findings extend to patients taking these drugs for obesity (higher doses, potentially different risk profile)?

Common questions

Read the original research

Do Incretin-Based Therapies Influence the Risk of Cholangiocarcinoma in Type 2 Diabetes Patients? Insights from a Systematic Review and Meta-Analysis.

Journal of gastrointestinal cancer, 56(1), 198

Citation

Yonatan, Eric Ricardo; Jusni, Louis Fabio Jonathan; Alvianto, Steven; Widjanarko, Nicolas Daniel; Usman, Steven Yulius; Muzellina, Virly Nanda. (2025). Do Incretin-Based Therapies Influence the Risk of Cholangiocarcinoma in Type 2 Diabetes Patients? Insights from a Systematic Review and Meta-Analysis.. Journal of gastrointestinal cancer, 56(1), 198. https://doi.org/10.1007/s12029-025-01330-9