GLP-1 receptor agonists are associated with a lower risk for hysterectomy in endometrial intraepithelial neoplasia/early-stage endometrial cancer (EIN/EC) when added to standard progestin therapy, according to a propensity score-matched cohort study.

“Our findings suggest a potential role of GLP-1 RAs [GLP-1 receptor agonists] as adjunctive metabolic therapy in fertility-sparing management. However, prospective studies and clinical trials are needed to evaluate effectiveness,” said lead investigator Tina Yi-Jin Hsieh, MD, while presenting the results at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer 2026.

Obesity is a risk factor for EIN/EC and also increases the risk for treatment failure and subsequent hysterectomy during progestin therapy.

Even so, there’s been scant research on the impact of GLP-1 RAs — widely used for weight loss — on outcomes, said Hsieh, who is a research fellow at Beth Israel Deaconess Medical Center, Boston.

The investigators used the TriNetX database to identify over 19,000 women diagnosed with EIN/EC before age 45 across the US from 2017 to 2024.

They then identified women treated with standard progestin therapy (oral agents or a progestin intrauterine device [IUD]) alone and those treated with progestins plus GLP-1 RAs, and used propensity scoring to create 432 matched pairs based on demographics, BMI, A1c, type 2 diabetes, hypertension, ischemic heart disease, stroke, healthcare utilization, and use of antidiabetics and estrogen.

Almost 70% had a BMI of 30.

GLP-1 RAs were strongly associated with a lower risk for hysterectomy.

At 6 months, hysterectomy rates were 6.5% in the GLP-1 group compared with 17.8% in the control group, corresponding to a 66% lower risk for hysterectomy. At 12 months, the risk was 62% lower, and at 18 months, it was 59% lower.

The association was even more pronounced in women younger than 40, with a 74%, 63%, and 60% lower risk for hysterectomy at 6, 12, and 18 months, respectively. The findings held whether women had EIN/EC.

“This is the first real-world data suggesting GLP-1 receptor agonists may improve outcomes in fertility-sparing management and supports the potential role of metabolic therapy as an adjunct to hormonal therapy,” said study discussant Brian Slomovitz, MD, gynecologic oncologist at Mount Sinai Medical Center, Miami.

However, there were no data on histologic response, reproductive outcomes, treatment duration, or long-term oncologic endpoints. It was also not reported whether progestin IUD use — which is associated with lower hysterectomy rates than oral progestins — was balanced between the groups.

As a result, Slomovitz agreed with the lead investigator: “Prospective studies are needed to further develop this in the treatment of endometrial cancer.”

A handful of early-phase, single-arm prospective studies are in the works.

There was no external reporting for the study, and Hsieh had no disclosures. Slomovitz declared being an advisor for GLP-1 RA-maker AstraZeneca, as well as for GSK, Merck, and other companies.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@medscape.net.