Background: Androgen-deprivation therapy (ADT) in prostate cancer (PC) decreases insulin sensitivity and increases the risk of the metabolic syndrome (MS). This study assessed the effects of metformin in abrogating ADT-induced insulin resistance. Methods: In a prospective 12-month study, men beginning ADT and with no history of diabetes mellitus (DM) received metformin for 6 months, followed by no metformin for a further 6 months. The primary outcome measures were the effect of metformin on the Homeostasis Model Assessment of Insulin Resistance (HOMA_IR) and the Whole Body Insulin Sensitivity Index (WB-ISI). The incidence of MS and related laboratory and anthropometric measures were also assessed. Results: Twenty-seven patients received ADT and metformin. Median age was 69 years. While all had normal fasting glucose at baseline, 11 (40.7%) had evidence of DM on oral glucose tolerance testing (OGTT). Eleven (40.7%) patients also had MS at baseline. Despite ADT, HOMA_IR remained stable during metformin therapy [1.7 (SEM±0.35) at baseline; 1.9 (SEM±0.32) at 6 months; P=0.18]; but increased once metformin was ceased [3.6 (SEM±2.2) at 12 months; P=0.07]. There was a significant fall in WB-ISI irrespective of metformin [7.4 (SEM±1.0) at baseline; 6.0 (SEM±0.79) at 6 months; 5.2 (SEM±1.6) at 12 months; P<0.01].  The number of patients with MS remained unchanged during metformin therapy, but 2 further patients developed MS at 12 months. Short-term metformin had no effect on blood pressure or other anthropometric measures, including waist circumference and body mass index, but did improve HDL cholesterol. Conclusions: Metformin may offset MS in men on ADT. Metformin had greater impact on fasting metabolic parameters (as measured by HOMA_IR) compared to its effect after a glucose load (as measured by WB-ISI). Importantly, this study found that a large proportion of PC patients had unsuspected MS and DM, suggesting a role for OGTT in all patients starting ADT.