This systematic review and meta-analysis examined the association between GLP-1RA or GIP/GLP-1 receptor co-agonist use and obesity-related cancer risk in adults (≥18 years) with type 2 diabetes mellitus and/or obesity. The analysis pooled data from 3,960,974 patients, with follow-up within ten years. The comparator was not reported in the input data.
The primary outcome was the overall risk of obesity-related cancers within ten years. The main finding was a significantly lower overall risk, with a relative risk (RR) of 0.70 (95% CI 0.54-0.89). For secondary outcomes, reduced risks were reported for hepatocellular carcinoma, colorectal, pancreatic, endometrial, esophageal, gallbladder, and ovarian cancers, and multiple myeloma. No significant association was found for thyroid cancer. Absolute numbers for these outcomes were not reported.
Safety and tolerability data were not reported. Key limitations of the included studies were not reported in the summary input. The analysis included both observational studies and randomized controlled trials, and the authors note prospective studies are required to validate the findings. The evidence shows an association, not causation, and the clinical relevance for practice should be interpreted with caution pending further prospective validation.
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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.