Diabetes Drugs and Hormonal Therapy May Lower Endometrial Cancer Risk

Recent research suggests weight loss medications could significantly reduce endometrial cancer risk and need for hysterectomy.

Published on Feb. 21, 2026

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A new study found that using GLP-1 receptor agonists like semaglutide and tirzepatide in combination with progestative therapy can lower the risk of endometrial cancer by 66% compared to progestatives alone. The research also indicated a decreased need for hysterectomy in these patients. Experts say this could lead to changes in treatment protocols and preventative care strategies for this common and aggressive cancer.

Why it matters

Endometrial cancer is the most prevalent gynecologic cancer, and obesity and diabetes are known risk factors. Traditional treatments like progestatives don't directly address these underlying metabolic issues. This research explores whether adding weight loss medications to progestative therapy can offer a more comprehensive approach to prevention and treatment.

The details

The retrospective study analyzed data from over 444,820 women and found that patients on the combined GLP-1RA and progestative therapy experienced a 66% lower risk of developing endometrial cancer compared to those treated with progestatives alone. The study also indicated a decreased need for hysterectomy, with a 53% lower risk at two years and a 41% lower risk at five years for those on the combined therapy.

  • The study was published in JAMA Network Open in February 2026.

The players

GLP-1 receptor agonists (GLP-1RAs)

Medications originally developed to treat type 2 diabetes that work by mimicking a natural hormone to help regulate blood sugar and promote weight loss.

Semaglutide

A GLP-1RA medication.

Tirzepatide

A GLP-1RA medication.

Progestatives

Commonly used to treat precancerous thickening of the uterine lining and abnormal uterine bleeding.

Metformin

A common diabetes medication.

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What’s next

Clinical trials are underway to further investigate the benefits of GLP-1RAs for endometrial cancer prevention and treatment, including NCI-2025-00102 examining tirzepatide or semaglutide for weight loss in endometrial cancer patients, and a pilot study at Memorial Sloan Kettering Cancer Center evaluating dual GIP/GLP-1 receptor agonist therapy.

The takeaway

This research suggests that adding weight loss medications like GLP-1 agonists to traditional progestative therapy could provide a more comprehensive approach to preventing endometrial cancer and reducing the need for hysterectomy in women with uterine conditions. However, further prospective studies and clinical trials are needed to confirm these findings and establish clear guidelines for clinical practice.