Tirzepatide for fertility-sparing treatment in obese/overweight patients with endometrial cancer and atypical hyperplasia: a phase II single-arm clinical trial protocol.

INTRODUCTION: Approximately 3-5% of patients with endometrial cancer (EC) are diagnosed under the age of 40 years, with 70% of these individuals being nulliparous. Consequently, fertility-sparing treatment for eligible young patients with endometrial lesions is increasingly being accepted. Obesity is a well-known factor closely associated with the incidence and prognosis of endometrial lesions. As obesity rates rise, weight loss interventions become particularly important in the treatment of these patients. Tirzepatide is currently the most effective glucagon-like peptide-1 receptor agonist for weight control. This trial aims to explore the synergistic effects and safety of tirzepatide combined with standard fertility-preserving treatment for endometrial lesions. METHODS AND ANALYSIS: This single-arm, phase II clinical trial aims to evaluate the efficacy and safety profile of tirzepatide as an adjunctive therapy to standard fertility-sparing treatment in obese or overweight patients with atypical hyperplasia (AH) or EC. The study will enrol a total of 45 patients, each receiving a combination of standard fertility-sparing treatment for EC and AH alongside tirzepatide. The primary outcomes include the reversal rate and time to remission (in months) of endometrial lesions, which are determined through endometrial pathology sampling every 3 months, as well as the percentage of weight reduction. Secondary objectives include evaluating changes in body morphology and composition, alterations in metabolic parameters during the study, as well as reproductive outcomes and the rate of tumour recurrence during follow-up. ETHICS AND DISSEMINATION: This study has received approval from the Ethics Committee of Peking Union Medical College Hospital (I-25PJ1055). Written informed consent will be obtained from all participants. The trial results will be disseminated through peer-reviewed medical journals and presented at an academic conference. TRIAL REGISTRATION NUMBER: ChiCTR2500102009.