GLP-1 Receptor Agonists Combined With Hormone Therapy Linked to Lower Endometrial Cancer Risk

A real-world retrospective study suggests that combining glucagon-like peptide-1 receptor agonists (GLP-1RA) with hormone therapy may lower the risk of endometrial cancer (EC) in women with endometrial hyperplasia (EH) or other benign gynecologic conditions. The addition of GLP-1RA to progestin-based therapy is associated with a statistically significant reduction in EC incidence across multiple treatment comparisons. This study was presented at the Society of Gynecologic Oncology 2025 Annual Meeting on Women’s Cancer.

Hormone therapy, including progestin-containing intrauterine devices (pIUD) and megestrol acetate (MA), is commonly used to manage EH, endometrial polyps, and abnormal uterine bleeding (AUB). However, some patients remain at risk for EC despite treatment. This study evaluates whether GLP-1RA, a class of medications commonly used for diabetes and weight management, further reduces EC risk when added to standard hormone therapy.

Researchers conducted a retrospective cohort study using TriNetX, a global federated research network encompassing electronic health records from 94 large healthcare organizations. Women aged ≥12 years diagnosed with EH, endometrial polyps, or AUB between May 2005 and August 2024 who received either pIUD or MA were included. Three propensity score-matched cohorts were created to compare EC risks: (1) GLP-1RA and pIUD versus pIUD-only, (2) GLP-1RA and MA versus MA-only, and (3) GLP-1RA and pIUD versus metformin and pIUD. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated.

In cohort 1, GLP-1RA plus pIUD was associated with a significant reduction in EC incidence compared with pIUD alone (HR = 0.44; 95% CI, 0.24-0.79). In cohort 2, GLP-1RA plus MA significantly reduced EC risk compared with MA alone (HR = 0.56; 95% CI, 0.38-0.81). In cohort 3, GLP-1RA plus pIUD was linked to a lower EC incidence versus metformin plus pIUD (HR = 0.33; 95% CI, 0.11-0.99). Among patients treated for AUB with pIUD, EC incidence was lower with the addition of GLP-1RA (0.19%) compared with pIUD alone (0.45%; HR = 0.48; 95% CI, 0.27-0.86). However, this risk reduction was not observed in patients with EH or endometrial polyps.

“Adding GLP-1RA to progestin therapy may be associated with a decreased risk of EC,” the authors concluded. “Further investigation is warranted to determine the potential applicability of GLP-1RA in this setting.”

Reference
Yen TT. Comparative effects of glucagon-like peptide-1 receptor agonists combined with hormone therapy on endometrial cancer risk among women with benign uterine or endometrial hyperplasia: A United States real-world retrospective study. Paper presented at: Society of Gynecologic Oncology 2025 Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Accessed March 11, 2025. https://www.sgo.org/events/annual-meeting/