Incretin-Based Drugs and the Incidence of Endometrial Cancer Among People with Type 2 Diabetes: Active Comparator New-User Design

Sonny M. Rothman, Hui Yin, Oriana H. Y. Yu, Michael Pollak and Laurent Azoulay ()
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Sonny M. Rothman: Lady Davis Institute, Jewish General Hospital
Hui Yin: Lady Davis Institute, Jewish General Hospital
Oriana H. Y. Yu: Lady Davis Institute, Jewish General Hospital
Michael Pollak: Lady Davis Institute of Medical Research, Jewish General Hospital, McGill University
Laurent Azoulay: Lady Davis Institute, Jewish General Hospital

Drug Safety, 2025, vol. 48, issue 9, No 5, 1023-1033

Abstract: Abstract Introduction The use of incretin-based drugs may be associated with a decreased risk of endometrial cancer among women with type 2 diabetes. Methods Using data from the UK Clinical Practice Research Datalink and linked databases, two new-user active comparator cohorts of women with type 2 diabetes who initiated glucagon-like peptide 1 receptor agonists (GLP-1 RAs) or sulfonylureas (cohort 1) and DPP-4 inhibitors or sulfonylureas (cohort 2) were assembled. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident endometrial cancer. Results Cohort 1 included 9239 new users of GLP-1 RAs and 80,086 new users of sulfonylureas. The GLP-1 RAs were not associated with a decreased risk of endometrial cancer when compared with sulfonylureas (HR: 1.11, 95% CI: 0.66–1.88). In a duration-response secondary analysis, use of GLP-1 RAs for more than two years was associated with an increased risk of endometrial cancer (HR: 2.47, 95% CI: 1.37–4.43) when compared to sulfonylureas When analysed by drug type, exenatide was associated with an elevated risk when compared to sulfonylureas (HR: 2.26, 95% CI:1.06–4.82). Cohort 2 included 42,486 new users of DPP-4 inhibitors and 79,353 new users of sulfonylureas. DPP-4 inhibitors were not associated with a decreased risk of endometrial cancer compared with sulfonylureas (HR: 1.00, 95% CI: 0.76–1.32). In a duration-response secondary analysis, use of DPP-4 inhibitors for more than two years was associated with an increased risk of endometrial cancer (HR: 1.63, 95% CI: 1.14–2.33) when compared to sulfonylureas. Conclusions In this population-based study, the use of GLP-1 RAs and DPP-4 inhibitors was not associated with a decreased risk of endometrial cancer when compared with the use of sulfonylureas among women with type 2 diabetes.

Date: 2025
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DOI: 10.1007/s40264-025-01551-8

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