A Study of Weight Loss Intervention With Tirzepatide and Progestin Intrauterine Device to Treat Endometrial Hyperplasia and Grade 1 Endometrial Cancer

This phase II trial studies whether adding tirzepatide injections to a levonorgestrel intrauterine device (LNG-IUD) improves pathologic response (absence of cancer cells in tissue samples after treatment) in women with endometrial atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or grade 1 endometrial cancer who are overweight or obese. Endometrial cancer occurrence has continued to rise in the United States. Over half of endometrial cancer cases are thought to be attributable to being overweight and obese, and the risk relationship appears to be weight dependent. AH/EIN is a precancerous condition of the endometrium (the uterus or womb) where the lining of the uterus grows abnormally thick, and the cells become abnormal. Women with this thickening have a higher-than-average risk of developing endometrial cancer if left untreated. The usual approach for patients who have AH/EIN and grade 1 endometrial cancer is the removal of the uterus. While surgical treatment is generally safe and effective, it may not be the best approach for some patients. The LNG-IUD is a small, T-shaped device inserted into the uterus that releases the hormone levonorgestrel, a progestin, which counteracts the effects of estrogen in the endometrium. Tirzepatide is a dual glucagon-like peptide 1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) agonist which has been shown to drive weight loss. Adding tirzepatide injections to LNG-IUD may help overweight or obese women with AH-EIN or grade 1 endometrial cancer lose weight, which may improve pathologic response.

NCT Number	NCT07349641
Lead Sponsor	National Cancer Institute (NCI)
Conditions	Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia, FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma
Enrollment	55 participants
Start Date	2026-07-06
Primary Completion	2028-12-31 (estimated)
Study Completion	2029-12-31 (estimated)
Updated on ClinicalTrials.gov	2026-07-27