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Associations Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Cancer Risk: A Systematic Review and
Isha Lalani1, Reynaldo Nambayan1, Chantelle Carbonell2
1Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Abstract:
IntroductionUse of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for control of type 2 diabetes and cardiovascular disease (CVD) risk reduction is increasing. Given the established link between obesity and multiple cancers, there is growing interest in the potential effects of GLP-1RAs on cancer risk reduction. This systematic literature review and meta-analysis evaluated the association between GLP-1RA use and cancer incidence.MethodsWe conducted literature searches in MEDLINE and EMBASE databases, covering publications up to September 17th, 2025. Our review included studies among adults receiving GLP-1RAs for any indication that reported effects on cancer incidence of any type.ResultsAmong 1,644 unique citations identified, 139 studies met the inclusion criteria for full-text review. After study exclusion, a total of 78 observational studies were included in the review and meta-analysis. GLP-1RA use was associated with statistically significant reductions in cancer risk for 10 of 13 obesity-associated cancers, specifically colorectal, endometrial, esophageal, gallbladder, liver, ovarian, pancreatic and stomach cancers along with meningioma and multiple myeloma. Compared to insulin specifically, GLP-1RAs provided protective effects against cancer of the colorectum (RR: 0.54, 95% CI: 0.44, 0.66), liver (RR: 0.35, 95% CI: 0.20, 0.62), and pancreas (RR: 0.41, 95% CI: 0.36, 0.48). The risk of developing thyroid cancer was slightly elevated, but not statistically significant, among GLP-1RA users (RR: 1.09, 95% CI: 0.98, 1.21).ConclusionsPooled estimates of observational studies suggest notable reductions in cancer incidence for several obesity-associated cancers. As GLP-1RA use increases, ongoing safety monitoring and long-term real-world data are essential. The potential role of GLP-1RAs in cancer risk reduction warrants further investigation through large-scale RCTs, alongside balanced risk-benefit discussions with patients.
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