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Glucagon-like peptide 1 receptor agonists and cancer risk: the good, the bad and the unknown

Nature Reviews Clinical Oncology (2026)Cite this article

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Abstract

Glucagon-like peptide 1 receptor agonists (GLP1RAs) are widely used for the treatment of type 2 diabetes mellitus (T2DM) and, at higher doses, obesity. Both T2DM and obesity are associated with a higher risk of cancer, which can be reduced by intentional weight loss, whereas effects of a reduction in hyperglycaemia are uncertain. GLP1RAs might have further direct effects, either beneficial or detrimental, on the development of specific malignancies. Evidence from preclinical and clinical studies suggests heterogeneous effects of GLP1RAs on cancer risk: the incidence of hepatocellular, oesophageal, endometrial, ovarian and prostate cancers might be reduced, whereas safety concerns persist with respect to thyroid (both medullary and non-medullary) carcinomas. Conversely, initial concerns on the risk of pancreatic cancer have not been confirmed. Nonetheless, the interpretation of current data is limited by detection and prescription biases in observational studies as well as insufficient follow-up and number of events in randomized trials. In this Review, we summarize current preclinical and clinical evidence, showing that the risk–benefit profile of GLP1RAs remains favourable in individuals with T2DM and obesity, although caution is warranted in those with a low cardiometabolic risk, for whom the potential risks of cancer might outweigh any expected benefits; conversely, the potential use of GLP1RAs as adjuvant therapies for certain forms of cancer needs to be further investigated.

Key points

  • The weight loss induced by glucagon-like peptide receptor 1 agonists (GLP1RAs) should reduce the risk of some malignancies, although stimulation of GLP1 receptors might have either detrimental or beneficial direct effects on cancer risk.

  • Early experimental data raised concerns of a possible risk of medullary thyroid carcinoma, whereas data from randomized trials suggest a possible increase in risk of non-medullary thyroid carcinoma.

  • Previous concerns regarding an association between GLP1RAs and pancreatic cancer have not been confirmed by data from epidemiological studies or randomized trials.

  • Accumulating evidence supports a possible reduction in risk of hepatocellular carcinoma as well as oesophageal, endometrial, prostate and ovarian cancers in those receiving GLP1RAs.

  • Methodological limitations of the available observational studies and randomized trials preclude definitive conclusions regarding the effects of GLP1RAs on the risk of various different malignancies.

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Fig. 1: Biological actions of GLP1.
Fig. 2: Preclinical and clinical evidence supporting an association of GLP1RAs with cancer risk.
Fig. 3: Potential effects of GLP1RAs on pancreatic cancer risk.
Fig. 4: Potential effects of GLP1RAs on the risk of hepatocellular carcinoma.

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  1. Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy

    Edoardo Mannucci & Ilaria Dicembrini

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E.M. has acted as a consultant of Boehringer Ingelheim, Dexcom, Eli Lilly, Novo Nordisk and Sanofi and received speaking fees from Eli Lilly, Novo Nordisk and Sanofi. I.D. has acted as a consultant of Medtronic, Novo Nordisk and Sanofi and received speaking fees from Abbott, Eli Lilly, Medtronic, MOVI, Novo Nordisk and Sanofi.

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Mannucci, E., Dicembrini, I. Glucagon-like peptide 1 receptor agonists and cancer risk: the good, the bad and the unknown. Nat Rev Clin Oncol (2026). https://doi.org/10.1038/s41571-026-01135-0

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