Tirzepatide Investigated for Endometrial Cancer Treatment in Overweight Women, Aiming for Fertility Preservation

Endometrial cancer (EC) and its precursor, endometrial intraepithelial neoplasia (EIN), are increasingly prevalent, particularly in women with obesity. Current standard treatment often involves hysterectomy, which is curative but eliminates fertility. For women desiring fertility preservation, progestin-based therapies like the levonorgestrel-releasing intrauterine device (LNG-IUD) are used, but efficacy can be suboptimal, especially in obese patients. There's a critical need for novel, non-surgical interventions that enhance disease regression while also addressing underlying metabolic comorbidities associated with obesity, which contribute to EC risk.

This Phase 2 randomized controlled trial (NCT07078838) will enroll overweight women diagnosed with EIN or Grade 1 endometrial cancer. Participants will be randomized into two groups: Group 1 receives the standard Progesterone IUD (LNG-IUD) plus Tirzepatide injections, while Group 2 receives the Progesterone IUD only. The study aims to compare the efficacy of adding Tirzepatide to standard care. Uterine tissue samples (biopsies) will be taken at baseline and 12 months to assess the primary endpoint of complete remission. Participants will also complete regular surveys to monitor quality of life, weight changes, and side effects.

This study describes an ongoing Phase 2 randomized controlled trial, thus no results are available yet. Researchers hypothesize that Tirzepatide may combat endometrial cancer through a dual mechanism: indirectly, by improving overall metabolic health and inducing significant weight loss, and directly, by potentially acting on abnormal uterine cells. The primary endpoint is the rate of complete remission of EIN or Grade 1 EC at 12 months, confirmed by histopathological analysis of uterine biopsies. Secondary endpoints include changes in body weight, metabolic markers, patient-reported quality of life, and the safety profile of Tirzepatide in this population. The trial aims to determine if the addition of Tirzepatide to standard LNG-IUD therapy significantly increases the rate of disease regression, offering a new therapeutic avenue. The study design ensures identical schedules for visits, tests, and monitoring across both groups.