Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

 Effects of four years testosterone treatment on glycaemia, anthropometry, quality of life and safety: The T4DM RUN-ON sub-study. (143735)

Gary Wittert 1 , Annelise Decaria 2 , Carolyn Allan 3 , Karen Bracken 4 , Mathis Grossmann 5 , David Handelsman 6 , Warrick Inder 7 , Andrzej Januszewski 8 , Alicia Jenkins 9 , David Jesudason 10 , Bronwyn Stuckey 11 , Bu B Yeap 12 , Kristy Robledo 2
  1. Adelaide University, North Terrace, SA, Australia
  2. Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
  3. Hudson Institute of Medical Research, Monash University, Clayton, Victoria, Australia
  4. Sydney Musculoskeletal Health , University of Sydney, Sydney, NSW, Australia
  5. Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
  6. ANZAC Research Institute, University of Sydney, Concord, NSA, Australia
  7. Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
  8. School of Pharmacy, University of Sydney, Sydney, NSW, Australia
  9. The Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
  10. Endocrinology, The Queen Elizabeth Hospital, Adelaide, SA, Australia
  11. Keogh Institute for Medical Research, Sir Charles Gardiner Hospital, Perth, WA, Australia
  12. Medical School, University of Western Australia, Perth, WA, Australia

Background: The T4DM trial showed that, in men aged ≥50 years with waist circumference> 95 cm and impaired glucose tolerance or newly diagnosed type 2 diabetes (T2D), two years of testosterone plus a lifestyle intervention reduced T2D risk by 40% versus lifestyle alone, with reduced fat mass, increased lean mass and strength, and improved sexual function.

Objective: To assess the durability of testosterone effects on glycemia, anthropometric measures, quality of life, sexual function, and safety over 4 years.

Methods: The T4DM RUNON sub-study extended the randomised, double-blind, placebo-controlled T4DM trial (n=1007) by two years, allowing up to four years of treatment. Eligible consenting participants (n=121) continued masked intramuscular testosterone undecanoate (n=65) (1000mg 3 monthly) or placebo (n=59) without the lifestyle program. Primary outcomes were 2-hr OGTT glucose and fasting plasma glucose. Secondary outcomes included anthropometry, grip strength, sexual function, health-related quality of life, and safety.

Results: Testosterone produced sustained glycaemic reductions over four years: mean difference in 2-hr OGTT glucose –1.0 mmol/L (95% CI –1.7 to –0.88) and fasting plasma glucose –0.26 mmol/L (95% CI –0.49 to –0.03), with most benefit during the first two years. The treatment effect on the proportion with 2-hr OGTT>11.1mmol/L at 2-years (P=0.011) was absent at 4-years (P=0.5).Adjusted mean differences in weight and waist circumference at 4 years were -1.3 kg (95% CI: -4.8 to 2.2) and –2.3 cm (95% CI: -5.4 to 0.7), respectively, with attenuation over time. Improved sexual desire at two years was maintained at four years, but other domains were not. Quality of life did not differ. No new safety concerns emerged, although hematocrit and haemoglobin increased further with testosterone (P<0.001).

Conclusions: In men with prediabetes or early T2D, prolonged testosterone treatment showed diminishing glycaemic benefits but durable improvements in anthropometry and sexual desire, with an acceptable safety profile.