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Reproductive Endocrinology

ORF09-06 - Effects of 4 Years Testosterone Treatment on Glycemia, Anthropometry, Sexual Function and Safety

Saturday, June 13, 2026
2:30 PM - 2:45 PM CT
Location: Room W185ABC
Disclosure(s):
Gary A. Wittert, MBBch, MD, FRACP: Besin: Consultant (); Lilly: Speakers' Bureau (); Novo Nordisk: Speakers' Bureau (); Opella: Advisory Board ()

The T4DM trial found that in men aged 50 years and older with waist circumference (WC) ≥ 95cm and impaired glucose tolerance, 2 years treatment with testosterone (T) (vs placebo) together with a lifestyle program reduced the risk of type 2 diabetes (T2DM) diagnosis at 2 years by 40% compared with a lifestyle program alone (1). This effect was associated with a greater reduction in fat mass, increased skeletal muscle mass and strength and improved sexual function.
To evaluate the durability of T treatment effects on glycemia, anthropometry, sexual function, quality of life, and safety over four years, the T4DM RUNON sub-study extended the T4DM randomized, double-blind, placebo-controlled trial (n=1007) by 2 years, for a total of up to 4 years of treatment, without ongoing enrolment in the lifestyle program. Eligible and consenting participants (n=121) continued their original masked allocation to intramuscular testosterone undecanoate (1000mg 3 monthly) or placebo. Primary outcomes were glycemia (2-hour OGTT and fasting plasma glucose). Secondary outcomes included anthropometry, sexual function (IIEF), health-related quality of life (SF36), and safety measures.
The effect of T treatment on glycemia over 4 years was sustained as measured by mean difference in 2-hr OGTT glucose ( –1.0 mmol/L, 95% CI –1.7 to –0.88); fasting plasma glucose (–0.26 mmol/L, 95% CI –0.49 to –0.03) with most benefit in the first 2 years. For the proportion with 2-hr OGTT >11.1mmol/L a significant treatment effect at 2-years (P=0.27), was absent at 4-years (P=0.5). The 4-year adjusted mean differences in weight and WC between the T and placebo groups were -1.3kg (95% CI: -4.8 to 2.2) and –2.3cm (95%CI: -5.4 to 0.7), respectively. Most benefit occurred within the first 2 years. The improvement in sexual desire at 2 years, but not of other domains of sexual function, was maintained at 4 years (mean difference 0.77 points, p< 0.001). Overall, quality of life was similar between T treatment and control groups over the 4 years. No further study withdrawals or new safety concerns emerged although hematocrit and hemoglobin increased further over time with T treatment (P < 0.001).
In men with prediabetes or early T2DM, in the subgroup with continuing blinded T treatment for up to 4 years there were diminishing glycemic benefits and durable improvements in anthropometry and sexual desire, with an acceptable safety profile.
Wittert, G. et al. Lancet Diabetes Endocrinol 9, 32-45 (2021).