Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM): Design and implementation of a double-blind randomised controlled trial.

Abstract

Low circulating testosterone is associated with an increased risk of developing type 2 diabetes (T2DM) in overweight men with impaired glucose tolerance (IGT). To determine in a multi-centre, double-blinded placebo-controlled randomised trial, whether testosterone treatment combined with lifestyle intervention (Weight Watchers®) relative to lifestyle intervention alone, reduces T2DM incidence and improves glucose tolerance at 2 years. Overweight or obese men aged 50-74 years with a serum testosterone of ≤14nmol/L and IGT or newly diagnosed T2DM established by an oral glucose tolerance test (OGTT). Six Australian capital city-based tertiary care centres. Participants were randomised 1:1 and injected with testosterone undecanoate (Reandron, Bayer) (1000mg/4ml) or vehicle (4ml castor oil), at baseline, 6 weeks and 3-monthly thereafter. PRIMARY ENDPOINTS: (1) Proportion of participants with 2-hour OGTT ≥ 11.1 mmol/L at 2 years. (2) A difference at 2 years ≥ 0.6mmol/L in the mean 2-hour OGTT glucose between treatments. Fasting insulin, HbA1c, body composition, maximal handgrip strength; sexual function and lower urinary tract symptoms; serum sex steroids and sex hormone binding globulin; mood and psychosocial function; adherence to lifestyle intervention; and healthcare utilisation and costs. Overseen by an Independent Data Safety Monitoring Committee. Haematocrit, lipids, and prostate-specific antigen (PSA) are assessed 6-monthly and information relating to haematological, urological and cardiovascular adverse events from each clinic visit. SUB-STUDIES: (i) Changes in bone density and micro-architecture; (ii) motivation and behaviour; (iii) telomere length; (iv) extended treatment up to 4 years, and (v) hypothalamo-pituitary testicular axis recovery at treatment end. This article is protected by copyright. All rights reserved.