Tirzepatide + LNG-IUD combination aims to improve pathologic response in overweight/obese endometrial cancer.

The incidence of endometrial cancer is rising, with over 50% of cases linked to overweight and obesity. Current standard-of-care for atypical endometrial hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or grade 1 endometrial cancer often involves hysterectomy, which may not suit all patients. Levonorgestrel intrauterine devices (LNG-IUDs) offer a progestin-based alternative by counteracting estrogen effects in the endometrium. Tirzepatide, a dual GLP-1/GIP agonist, is being investigated for its weight loss benefits, which could synergistically improve outcomes.

This Phase II trial will investigate tirzepatide injections combined with a levonorgestrel intrauterine device (LNG-IUD) in 30 overweight or obese women. Participants will have either atypical endometrial hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or grade 1 endometrial cancer. The primary endpoint is improved pathologic response, defined as the absence of cancer cells in tissue samples after treatment. The study aims to determine if tirzepatide's weight loss effects enhance the LNG-IUD's efficacy.

This is a not-yet-recruiting Phase II trial, so no direct findings are available. The study's premise is that tirzepatide, a dual GLP-1/GIP agonist known for driving weight loss, will enhance the therapeutic effect of the levonorgestrel intrauterine device (LNG-IUD). > Over 50% of endometrial cancer cases are attributed to overweight and obesity, suggesting a strong link between metabolic health and disease progression. The trial hypothesizes that weight loss induced by tirzepatide will improve the pathologic response in women with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or grade 1 endometrial cancer. The LNG-IUD counteracts estrogen's effects on the endometrium, and the combination aims for a synergistic effect to reduce cancer cells. The study anticipates enrolling 30 participants to evaluate this novel therapeutic strategy.