Testosterone Therapy to Prevent Type 2 Diabetes Mellitus in At-Risk Men (T4DM): Design and Implementation of a Double-Blind Randomised Controlled Trial
[Note: ASIH - SUB-STUDIES (v)]
BACKGROUND: Low circulating testosterone is associated with an increased risk of developing type 2 diabetes (T2DM) in overweight men with impaired glucose tolerance (IGT). A
IM: To determine in a multi-centre, double-blinded placebo-controlled randomised trial, whether testosterone treatment combined with lifestyle intervention (Weight Watchers(R)) 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 </=14nmol/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 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.
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 utilisation 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:
(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.
Wittert G, Atlantis E, Allan C, et al. Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM): Design and implementation of a double-blind randomised controlled trial. Diabetes, obesity & metabolism 2018. https://onlinelibrary.wiley.com/doi/abs/10.1111/dom.13601
[Note: ASIH - SUB-STUDIES (v)]
BACKGROUND: Low circulating testosterone is associated with an increased risk of developing type 2 diabetes (T2DM) in overweight men with impaired glucose tolerance (IGT). A
IM: To determine in a multi-centre, double-blinded placebo-controlled randomised trial, whether testosterone treatment combined with lifestyle intervention (Weight Watchers(R)) 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 </=14nmol/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 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.
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 utilisation 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:
(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.
Wittert G, Atlantis E, Allan C, et al. Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM): Design and implementation of a double-blind randomised controlled trial. Diabetes, obesity & metabolism 2018. https://onlinelibrary.wiley.com/doi/abs/10.1111/dom.13601
