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. 2025 Sep;68(9):1924-1936.
doi: 10.1007/s00125-025-06453-z. Epub 2025 Jun 5.

Glucagon-like peptide-1 receptor agonists and gastrointestinal cancer risk in individuals with type 2 diabetes

Chia-Chih Kuo  1 , Min-Hsiang Chuang  1 , Chun-Hsien Li  2 , Ya-Wen Tsai  3 , Po-Yu Huang  1 , Hsing-Tao Kuo  1   4 , Chih-Cheng Lai  5   6
Affiliations

Glucagon-like peptide-1 receptor agonists and gastrointestinal cancer risk in individuals with type 2 diabetes

Chia-Chih Kuo et al. Diabetologia. 2025 Sep.

Abstract

Aims/hypothesis: Although benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been demonstrated in treatment of type 2 diabetes and weight management, their potential role in cancer prevention remains inadequately explored.

Methods: Using the TriNetX Research Network, we conducted a retrospective cohort study comparing new users of GLP-1RAs with users of other glucose-lowering medications. Propensity score matching was performed for demographic factors, socioeconomic factors, family history, lifestyle factors and cancer risk factors. The primary outcome was the incidence of obesity-related gastrointestinal cancers, and secondary outcomes were the incidence of individual cancer types.

Results: Using adjusted HRs (aHRs), GLP-1RA use was found to be associated with a significantly lower risk of overall gastrointestinal cancer compared with all other glucose-lowering medications (insulin: aHR 0.29; 95% CI 0.23, 0.37; metformin: aHR 0.84; 95% CI 0.71, 0.99; sulfonylureas: aHR 0.71; 95% CI 0.62, 0.80; thiazolidinediones: aHR 0.86; 95% CI 0.74, 0.99; dipeptidyl peptidase-4 inhibitors: aHR 0.80; 95% CI 0.70, 0.91; sodium-glucose cotransporter-2 inhibitors: aHR 0.80; 95% CI 0.68, 0.96). The protective effect was most pronounced compared with insulin therapy, with significant risk reductions across all individual cancers.

Conclusions/interpretation: GLP-1RA use is associated with a reduced risk of gastrointestinal cancers in individuals with type 2 diabetes. These findings suggest potential cancer-protective benefits of GLP-1RAs beyond their established roles in glycaemic management and weight reduction.

Keywords: Cancer; Colorectal cancer; Diabetes; Gastrointestinal; Glucagon-like peptide-1 receptor agonist; Insulin.

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Conflict of interest statement

Data availability: The data utilised in this study were obtained from the TriNetX Research Network, a global federated health research platform providing access to de-identified electronic medical records from participating healthcare organisations. Due to data use agreements and privacy regulations, the individual-level data are not publicly available. However, aggregated data supporting the findings of this study can be accessed through the TriNetX platform by qualified researchers upon reasonable request and subject to approval by TriNetX. Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: C-CK and C-CL conceived and designed the study. C-CK and C-CL performed the statistical analysis, prepared the first draft of the manuscript, and revised the draft. All authors contributed to the interpretation of data and critically revised the content of the draft. C-CK and H-TK supervised the study. All authors gave final approval of the version to be published. As such, they had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. C-CL is the guarantor of this work.

References

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