Patients
Tumors, visceral disease, disability, diabetes
IMPAIRED GLUCOSE TOLERANCE, METASTATIC DISEASE, TUMORS, METASTATIC PROSTATE CANCER, DIABETES
Patients had histologically proven PC and an ECOG performance status of 0 to 2 (on a 5-point scale, with 0 indicating an absence of disability and higher numbers indicating greater disability). Patients required castration therapy with either an LHRH analogue (continuous) or surgical castration. Patient were permitted to use anti-androgen therapy prior to castration; with enrollment into study at the time of castration or within 30 days of castration. All patients were required to have baseline oral glucose tolerance test (OGTT) and patients with values of >200 mg/dL at 2 hours, suggesting a diagnosis of diabetes, were excluded from study and referred for treatment of diabetes. Patients with values between 140 mg/dL and 200 mg/dL indicating impaired glucose tolerance were permitted to enroll and advised dietary modification. Patients with normal values of less than 140 mg/dL were permitted to enroll.All patients with metastatic disease were documented through computed tomography (CT) or nuclear bone scan, according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Patients were excluded if they were being treated with any anti-hyperglycemic medications prior to study, had BUN, creatinine, bilirubin levels less than or equal to 1.3 times the upper limit of normal. Safety and dosing adherence were evaluated during each trial visit.Medical castration using gonadotropin-releasing hormone (GnRH) agonist for all subjects based on treating physician preference was done within 72 hours of an oral glucose tolerance test or baseline visit. Patients were randomly assigned in a 1:1 ratio to receive ADT with metformin (one 500 mg tablet TID) or color matched placebo (the placebo group). Patients were stratified according to the presence or absence of measurable visceral disease, PSA and ECOG performance status score (0 or 1 vs. 2). Metformin or placebo were allowed to be started within 72 hours of medical castration. Men who had previously started castration therapy for metastatic prostate cancer or biochemical flair were also permitted to enter study provided castration therapy was within 4–6 weeks of study entry.All patients who had not undergone surgical castration, received ongoing ADT to reach or maintain a serum testosterone level of less than 50 ng per deciliter (1.7 nmol per liter).