BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity are increasing and are established risk factors for malignancy. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for T2DM and obesity, but their association with cancer risk remains uncertain. We assessed the association between GLP-1RA use and obesity-related cancers.
METHODS: We searched Embase, PubMed, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 20 November 2025. Observational studies and randomized controlled trials of adults (≥18 years) with T2DM and/or obesity reporting cancer risk after GLP-1RA or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor co-agonist use were included. Obesity-related cancers comprised uterine, esophageal, thyroid, gastric, colorectal, liver, gallbladder, pancreatic, breast, ovarian, kidney cancers, cholangiocarcinoma, meningioma, and multiple myeloma.
FINDINGS: Twenty-four studies involving 3,960,974 patients were included. GLP-1RA use was associated with a significantly lower overall risk of obesity-related cancers within ten years (RR 0·70, 95% CI 0·54-0·89). Reduced risks were observed for hepatocellular carcinoma, colorectal, pancreatic, endometrial, esophageal, gallbladder, ovarian cancers, and multiple myeloma, with no significant association for thyroid cancer.
INTERPRETATION: GLP-1RA use is associated with a lower risk of several obesity-related cancers. Prospective studies are required to validate these findings and clarify underlying mechanisms.
