Preoperative Semaglutide Prior to Radical Prostatectomy

In this exploratory, single-arm, nonrandomized trial, the impact of the preoperative utilization of the glucagon-like peptide-1 (GLP-1) receptor agonist (RA) semaglutide prior to radical prostatectomy in participants with intermediate risk prostate cancer will be investigated. Semaglutide will be administered according to the FDA-approved label for chronic weight management and participants will be dosed with a weekly subcutaneous injection. The primary aim of this trial is to explore the tumor biological activity of semaglutide in these participants. The trial will also evaluate the safety and tolerability of this preoperative treatment, along with the impact on physiologic/metabolic parameters.

Inclusion Criteria: * Male participants aged ≥18 years * Biopsy-proven intermediate-risk localized prostate cancer per NCCN risk stratification criteria * Planning to undergo radical prostatectomy, and surgical delay of 3-6 months is deemed appropriate by the investigator * Body mass index (BMI) \>35 kg/m² * No prior exposure to androgen deprivation therapy or androgen receptor pathway inhibitors Exclusion Criteria: * Prostate cancer risk classification other than intermediate risk * Hemoglobin A1c (HbA1c) \>9% * Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2) * Baseline gastroparesis, dysphagia, or other significant gastrointestinal disease limiting oral intake * Current or recent (within 12 months) exposure to GLP-1 receptor agonist therapy * Delay of radical prostatectomy by 3-6 months is not deemed advisable by the investigator