Semaglutide, Weight Loss, and LNG-IUD for Conservative Treatment of Endometrial Atypical Hyperplasia and Grade 1 Endometrial Cancer

NCT07820358 · Not yet recruiting

Last updated 2026-09-22

This clinical trial is testing whether the medication semaglutide, combined with weight loss and a hormonal IUD, can help treat early-stage endometrial cancer or atypical hyperplasia in women who are overweight or obese.

Status Not yet recruiting Approved but enrollment has not started.

Phase Phase 2 Tests whether it works and watches safety in a moderate group.

Type Interventional (clinical trial)

Design open-label (no blinding) treatment study

Participants 48 people Planned (estimated).

Who can join Ages 18+ · female only

Timeline Started 2027-01 · est. completion 2031-12

Where 4 sites · United States

What this study is testing ClinicalTrials.gov NCT07820358 ↗

Description as written by the study sponsor.

The goal of this clinical trial is to learn if a combination treatment of a hormonal intrauterine device (LNG-IUD), semaglutide, and a structured weight loss program can treat endometrial atypical hyperplasia or grade 1 endometrioid endometrial cancer while preserving fertility in women of reproductive age with endometrial atypical hyperplasia (EAH) or FIGO grade 1 endometrioid endometrial cancer who wish to preserve their fertility. The main questions it aims to answer are: * What proportion of participants achieve a complete pathological response after treatment? * How durable is the response at 12 months? * What effect does the treatment have on metabolic outcomes (weight, BMI, HbA1c) and quality of life? Participants will: * Receive an LNG-IUD * Receive semaglutide 2.4mg * Participate in a structured weight loss program * Undergo hysteroscopy with endometrial sampling to assess treatment response * Complete quality-of-life assessments at baseline, 6 months, and 12 months

Treatments tested

Semaglutide (Wegovy) weekly injection Drug

Semaglutide 2.4 mg administered subcutaneously once weekly, following standard dose-escalation protocol, for the duration of the 6-month active treatment period. Used off-label in this trial for its metabolic effects in combination with LNG-IUD, rather than as monotherapy for weight loss.
LNG-IUD (Progestin) Device

Levonorgestrel-releasing intrauterine device inserted at study baseline and maintained through the active treatment and follow-up periods, providing continuous local progestin delivery to the endometrium in combination with systemic semaglutide.
Structured Weight Loss Program Behavioral

A structured, protocol-defined weight loss program combining dietary counseling and physical activity guidance, delivered concurrently with pharmacologic and device-based treatment to support metabolic response, distinct from weight loss achieved through semaglutide alone.

Main thing measured	Pathological Response Rate
Sponsor	The Methodist Hospital Research Institute
Conditions studied	Endometrial Atypical Hyperplasia, Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia, Endometrial Cancer Stage I, Endometrial Cancer, Fertility-Sparing Treatment (FST), Obesity & Overweight
GLP-1 drugs	semaglutide

Full protocol, eligibility, and contacts on ClinicalTrials.gov NCT07820358 ↗