Poster Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Testosterone for type 2 diabetes prevention in men: A 2-year multicentre, randomised, double-blind, placebo-controlled trial (#189)

Gary Wittert 1 , Evan Atlantis 1 2 , Mathis Grossmann 3 , Bu B Yeap 4 5 , Ann Conway 6 7 , Bronwyn Stuckey 8 , David Handelsman 6 7 , Robert McLachlan 9 10 , Carolyn Allan 9 10 , Alicia Jenkins 11 , Mark Daniel 12 13 , Karen Bracken 11
  1. School of Medicine, University of Adelaide, Adelaide, SA, Australia
  2. School of Nursing and Midwifery, Western Sydney University, Sydney, NSW, Australia
  3. Uiversity of Melbourne, Heidelberg, Vic, Australia
  4. School of Medicine, University of Western Australia, Perth, WA, Australia
  5. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia
  6. ANZAC Research Institute, Sydney, NSW, Australia
  7. Andrology Department, Concord Hospital, Sydney, NSW, Australia
  8. University of Western Australia, Perth, WA, Australia
  9. Hudson Institute of Medical Research, Melbourne, Vic, Australia
  10. Monash University, Melbourne, Vic, Australia
  11. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
  12. University of Melbourne, Melbourne, Vic, Australia
  13. University of Canberra, Canberra, ACT, Australia

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