Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for type 2 diabetes mellitus (T2DM) and overweight or obesity, but their association with cancer is unclear. PURPOSE: To investigate the risk for obesity-related cancer associated with GLP-1RAs. DATA SOURCES: PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials from inception to August 2025. STUDY SELECTION: Randomized placebo-controlled trials reporting any of the following cancer outcomes: thyroid, pancreatic, colorectal, gastric, esophageal, liver, gallbladder, breast, ovarian, endometrial, or kidney cancer; multiple myeloma; or meningioma. DATA EXTRACTION: Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool, and certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Odds ratios (ORs) were pooled using random-effects meta-analysis. DATA SYNTHESIS: The review included 48 trials involving 94 245 participants. GLP-1RAs probably have little or no effect on risk for thyroid cancer (OR, 1.37 [95% CI, 0.82 to 2.31]; 1 fewer to 9 more cases per 10 000 patients treated), pancreatic cancer (OR, 0.84 [CI, 0.53 to 1.35]; 9 fewer to 6 more per 10 000), breast cancer (OR, 0.95 [CI, 0.60 to 1.49]; 10 fewer to 12 more per 10 000), or kidney cancer (OR, 1.12 [CI, 0.78 to 1.60]; 5 fewer to 13 more per 10 000) (moderate certainty). GLP-1RAs may have little or no effect on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancer; multiple myeloma; or meningioma (low certainty). The effect on gastric cancer is very uncertain. Results were consistent in sensitivity analyses of trials with low risk of bias and studies of semaglutide or tirzepatide and across subgroups stratified by follow-up duration, population, GLP-1RA class, weight loss profile, dose, and duration of action. LIMITATION: The included trials were not designed to evaluate cancer outcomes and had short follow-up. CONCLUSION: GLP-1RAs may have little or no effect on risk for obesity-related cancers. Longer-term studies are needed to clarify potential risks or benefits. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42024608365).