Background: Low serum testosterone level is associated with increased risk of type 2 diabetes (T2D) in overweight men with impaired glucose tolerance (IGT). It is not known whether testosterone (T) treatment is effective and safe for preventing T2D in this high-risk group.
Aim: To determine in a large, multicentre, double-blinded placebo-controlled RCT, whether T treatment combined with lifestyle intervention (Weight Watchers®) as compared to lifestyle intervention alone, reduces T2D at 2 years.
Study population: Overweight or obese men aged 50-74 years with T ≤14nmol/L, and IGT or newly diagnosed T2D established by an oral glucose tolerance test (OGTT).
Setting, drug and protocol: Six Australian, capital city-based, tertiary care centres. Injectable testosterone undecanoate (Reandron, Bayer AG) (1000mg/4ml) or vehicle (4ml benzyl benzoate and castor oil only), 1:1 randomisation, at baseline, 6 weeks, and then 3 monthly thereafter. Randomisation stratified by centre, age group, 2-hour serum glucose, current smoking, and first-degree family history of T2D.
Primary endpoint: A non-diabetic 2-hour serum glucose (<11.1mmol/L) on a 75g OGTT at week 102. With 1000 participants, the study has 80% power for a 40% relative-risk reduction.
Secondary endpoints: Waist circumference, BMI, body composition (DEXA); fasting glucose, HbA1c, serum sex steroids and SHBG; peak hand grip strength; sexual function and lower urinary tract symptoms; mood and psychosocial function; adherence to the lifestyle intervention; and health care utilisation and costs. Blood for DNA and serum for markers of inflammation and metabolism will be stored.
Safety: An Independent Data Safety Monitoring Committee (IDSMC) with a focus on haematological, urological and cardiovascular events.
Sub-studies: Changes in bone microarchitecture (T4Bone); motivation and behaviour; telomere length; and effects of extended treatment for up to 4 years (T4DM run-on), and rate of recovery of the hypothalamo-pituitary testicular axis at treatment-end (T4DM run-off).
Trial Registration: ACTRN12612000287831. Funding: NH&MRC APP1030123