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

Sonny M Rothman^1,2, Hui Yin¹, Oriana H Y Yu^1,3,4

¹Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, H425.1, Montreal, Quebec, H3T 1E2, Canada.

|May 10, 2025

Summary

This summary is machine-generated.

Incretin-based drugs like GLP-1 RAs and DPP-4 inhibitors were not linked to reduced endometrial cancer risk in women with type 2 diabetes. Longer use, however, showed an increased risk for both drug classes compared to sulfonylureas.

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Area of Science:

Endocrinology
Oncology
Pharmacoepidemiology

Background:

Type 2 diabetes is common in women, and endometrial cancer is a significant concern.
Incretin-based therapies, including GLP-1 RAs and DPP-4 inhibitors, are widely used for type 2 diabetes management.
Previous research suggested a potential protective effect of these drugs against endometrial cancer.

Purpose of the Study:

To investigate the association between glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors with endometrial cancer risk.
To compare the risk of endometrial cancer in women with type 2 diabetes using GLP-1 RAs or DPP-4 inhibitors versus sulfonylureas.

Main Methods:

A population-based cohort study using UK Clinical Practice Research Datalink and linked databases.
Two cohorts were constructed: GLP-1 RAs vs. sulfonylureas, and DPP-4 inhibitors vs. sulfonylureas.
Propensity score methods were used to adjust for confounders and estimate hazard ratios for endometrial cancer.

Main Results:

GLP-1 RAs were not associated with a decreased risk of endometrial cancer compared to sulfonylureas (HR: 1.11).
Long-term use (>2 years) of GLP-1 RAs was linked to an increased risk (HR: 2.47), with exenatide showing an elevated risk (HR: 2.26).
DPP-4 inhibitors were not associated with a decreased risk (HR: 1.00), but long-term use (>2 years) showed an increased risk (HR: 1.63).

Conclusions:

Neither GLP-1 RAs nor DPP-4 inhibitors were associated with a reduced risk of endometrial cancer in women with type 2 diabetes when compared to sulfonylureas.
Prolonged use of these incretin-based drugs may be associated with an elevated risk of endometrial cancer.
These findings highlight the importance of considering drug duration and type in the context of endometrial cancer risk for diabetic patients.