Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM)

Design and implementation of a double-blind randomized controlled trial

Gary Wittert, Evan Atlantis, Carolyn Allan, Karen Bracken, Ann Conway, Mark Daniel, Val Gebski, Mathis Grossmann, Wendy Hague, David J Handelsman, Warrick Inder, Alicia Jenkins, Anthony Keech, Robert McLachlan, Kristy Robledo, Bronwyn Stuckey, Bu B Yeap

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND: Low circulating testosterone is associated with an increased risk of developing type 2 diabetes (T2DM) in overweight men with impaired glucose tolerance (IGT). AIMS: To determine in a multi-centre, double-blinded placebo-controlled randomized 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. STUDY POPULATION: Overweight or obese men aged 50-74 years with a serum testosterone of ≤14 nmol/L and IGT or newly diagnosed T2DM established by an oral glucose tolerance test (OGTT). SETTING, DRUG AND PROTOCOL: Six Australian capital city-based tertiary care centres. Participants were randomized 1:1 and injected with testosterone undecanoate (1000 mg/4 mL) or vehicle (4 mL castor oil), at baseline, 6 weeks and 3-monthly thereafter. PRIMARY ENDPOINTS: (a) Proportion of participants with 2-hour OGTT ≥11.1 mmol/L at 2 years, and (b) a difference at 2 years ≥0.6 mmol/L in the mean 2-hour OGTT glucose between treatments. SECONDARY ENDPOINTS: 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 utilization and costs. SAFETY: 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: (a) Changes in bone density and micro-architecture, (b) motivation and behaviour, (c) telomere length, (d) extended treatment up to 4 years, and (e) hypothalamo-pituitary testicular axis recovery at treatment end.

Original languageEnglish
Pages (from-to)772-780
Number of pages9
JournalDiabetes, Obesity and Metabolism
Volume21
Issue number4
Early online date2018
DOIs
Publication statusPublished - 1 Apr 2019

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Type 2 Diabetes Mellitus
Testosterone
Glucose Tolerance Test
Randomized Controlled Trials
Life Style
Glucose Intolerance
Clinical Trials Data Monitoring Committees
Castor Oil
Glucose
Sex Hormone-Binding Globulin
Lower Urinary Tract Symptoms
Telomere
Therapeutics
Prostate-Specific Antigen
Ambulatory Care
Body Composition
Serum
Hematocrit
Tertiary Care Centers
Health Care Costs

Cite this

Wittert, Gary ; Atlantis, Evan ; Allan, Carolyn ; Bracken, Karen ; Conway, Ann ; Daniel, Mark ; Gebski, Val ; Grossmann, Mathis ; Hague, Wendy ; Handelsman, David J ; Inder, Warrick ; Jenkins, Alicia ; Keech, Anthony ; McLachlan, Robert ; Robledo, Kristy ; Stuckey, Bronwyn ; Yeap, Bu B. / Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM) : Design and implementation of a double-blind randomized controlled trial. In: Diabetes, Obesity and Metabolism. 2019 ; Vol. 21, No. 4. pp. 772-780.
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Wittert, G, Atlantis, E, Allan, C, Bracken, K, Conway, A, Daniel, M, Gebski, V, Grossmann, M, Hague, W, Handelsman, DJ, Inder, W, Jenkins, A, Keech, A, McLachlan, R, Robledo, K, Stuckey, B & Yeap, BB 2019, 'Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM): Design and implementation of a double-blind randomized controlled trial', Diabetes, Obesity and Metabolism, vol. 21, no. 4, pp. 772-780. https://doi.org/10.1111/dom.13601

Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM) : Design and implementation of a double-blind randomized controlled trial. / Wittert, Gary; Atlantis, Evan; Allan, Carolyn; Bracken, Karen; Conway, Ann; Daniel, Mark; Gebski, Val; Grossmann, Mathis; Hague, Wendy; Handelsman, David J; Inder, Warrick; Jenkins, Alicia; Keech, Anthony; McLachlan, Robert; Robledo, Kristy; Stuckey, Bronwyn; Yeap, Bu B.

In: Diabetes, Obesity and Metabolism, Vol. 21, No. 4, 01.04.2019, p. 772-780.

Research output: Contribution to journalArticle

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AU - Grossmann, Mathis

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AU - Inder, Warrick

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AU - Keech, Anthony

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