Metformin can reduce cardiovascular risk factors in men treated with androgen deprivation therapy

Introduction and Objectives: Androgen deprivation therapy (ADT) is an essential component of treating men with advanced and metastatic prostate cancer. The treatment is associated with cardiovascular risk factors such as obesity, hypercholesterolaemia, and hyperglycaemia. In this single blinded prospective phase I multi-site randomized clinical trial, we assess the metabolic benefits of metformin compared to placebo in men starting ADT. Methods: Consecutive men with newly diagnosed metastatic prostate cancer who are not suitable or unwilling to undergo chemotherapy were recruited. Patients underwent physical and metabolic parameter assessment (glucose, lipids, insulin, leptin, adiponectin and ghrelin) and started on EligardTM 45 mg with 4 weeks of bicalutamide. At 3 months, patients were randomized into ADT + placebo or metformin treatment groups. Patients were followed up 6 weekly for 54 weeks. Results: 45 patients have been recruited into the clinical trial to date. 28 patients were diagnosed with metabolic syndrome and fourteen with diabetes, impaired fasting glucose or impaired glucose tolerance at the time of starting ADT. At a minimum of 3 months follow-up, 37 patients were available for analysis. Patients demonstrated percentage changes in weight by 0.14%, PSA -86.5%, total cholesterol 7.1%, triglyceride 30.6%, high density lipoprotein -2.9%, low density lipoprotein 17.3%, fasting glucose -10.8%, fasting insulin 10% and homeostatic model assessment-insulin resistance score 7%. 28 patients were available for analysis with 3 months following randomization (Visit5). Changes in BMI, total cholesterol, low density lipoprotein, glucose and insulin by -0.06%, -3.5%, 9.3%, -5% and -4% respectively were observed with metformin treatment compared to placebo. Conclusions: Treatment with metformin as an adjuvant therapy may be an effective strategy to negate the metabolic effects of ADT in men with newly diagnosed meta-static prostate cancer. In men with a previous history of cardiovascular disease, modest reduction in cardiovascular risk factors may be especially important. These findings provide grounds for a larger randomized clinical trial to assess overall survival of men treated with adjuvant metformin in addition to ADT.