Use of metformin and lifestyle intervention to prevent ADT-related metabolic syndrome in prostate cancer

Abstract

5159 Background: The association between androgen deprivation therapy (ADT) for prostate cancer and metabolic syndrome has been reported, with insulin resistance as the key to its development. This is the first study to investigate the effect of metformin and lifestyle changes on the development of ADT-related metabolic syndrome. Methods: Forty men with any stage of prostate cancer, due to receive ADT with a GnRH agonist, were recruited to a prospective randomised pilot study. The control arm comprised 20 patients receiving ADT alone. Men in the intervention arm (n=20) received ADT with 6 months of metformin, a low glycaemic index diet and a regular aerobic exercise programme. All patients were investigated pre-treatment and at 6 months for the metabolic syndrome, insulin resistance, and related biochemical and physical parameters. Results: After 6 months a significant reduction in metabolic syndrome cases (NCEP ATP III definition) was seen in the intervention arm (p=0.042), with an equal number seen in the control arm as at baseline. There was an increase in HDL cholesterol in both arms, which reached greater significance in the intervention arm (p=0.008) than the controls (p=0.015). The table shows an improvement in abdominal girth, weight, body mass index, and systolic blood pressure in the intervention arm, when measured as a % change over 6 months. Biochemical markers of insulin resistance did not significantly differ between each group. Conclusions: ADT is widely used in prostate cancer, but metabolic complications may be responsible for an increased cardiovascular mortality. The preventative role of metformin and lifestyle changes has been evaluated in this study, showing potential beneficial effects. However, the anticipated increased incidence of insulin resistance and metabolic syndrome has not been demonstrated in men receiving ADT alone, which may be due to small study size. Further studies will ascertain whether overall survival can ultimately be improved by this approach. [Table: see text] No significant financial relationships to disclose.