(052) Incretin-Based Drugs and the Incidence of Endometrial Cancer Among Patients with Type 2 Diabetes

Background: Experimental evidence suggests that incretin-based drugs may attenuate the growth of endometrial cancer cells in a dose-dependent manner. However, there is limited real-world evidence of this possible association.

Objectives: To determine whether the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, separately, is associated with a decreased risk of endometrial cancer.

Methods: Using data from the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episodes Statistics Admitted Patient Care and Office for National Statistics databases, we assembled a cohort of female patients with type 2 diabetes who were newly prescribed GLP-1 RAs, DPP-4 inhibitors or sulfonylureas from January 1, 2007 to December 31, 2021, with follow-up until December 31, 2022. We used a new user cohort design in which two separate cohorts were constructed: new users of GLP-1 RAs and sulfonylureas (Cohort 1) and new users of DPP-4 inhibitors and sulfonylureas (Cohort 2). Propensity score fine stratification weighting was used to balance the exposure groups. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for incident endometrial cancer using an on-treatment exposure definition with a one-year grace period to account for latent effects. Kaplan-Meier curves were constructed to assess the cumulative incidence of endometrial cancer in each exposure group over time.

Results: Cohort 1 included 9,239 new users of GLP-1 RAs and 80,086 new users of sulfonylureas. Compared with sulfonylureas, GLP-1 RAs were not associated with a decreased risk of endometrial cancer (IR 1.26 and 1.41, respectively; HR 1.11, 95% CI 0.66-1.88). Similar findings were observed in Cohort 2, where the use of DPP-4 inhibitors was not associated with a decreased risk compared with sulfonylureas (IR 1.38 and 1.38, respectively; HR 1.00, 95% CI 0.76-1.32). The Kaplan-Meier curves generated overlapping cumulative incidence curves in each cohort. Results remained consistent in secondary analyses except for exenatide (HR 2.66, 95% CI 1.06-4.82).

Conclusions: In this large, population-based study from the United Kingdom, GLP-1 RAs and DPP-4 inhibitors were not associated with a decreased risk of endometrial cancer.