Hypogonadism is associated with several health consequences, such as cardiovascular disease, obesity, diabetes, osteoporosis, quality of life, and even economic impacts.
Hypogonadism, commonly seen in overweight or obese men is associated with an increased risk of T2D.2 Observational studies have previously shown that testosterone treatment for men with hypogonadism improves metabolic parameters such as fasting glucose, insulin resistance, body composition resulting in the prevention of developing T2D, and may even revert T2D3-7. However, this was not yet confirmed with a randomized controlled trial. The T4DM Phase 3 study is the world’s first large-scale, placebo-controlled randomized trial assessing testosterone treatment for preventing or reversing T2D in overweight or obese men with low testosterone levels.
Study participants were men at high risk of T2D (pre-diabetes) or with newly-diagnosed T2D and low testosterone levels. They were enrolled in a community-based lifestyle program and randomized to receive intramuscular testosterone undecanoate 1000mg (504 men) or placebo (503 men) every 3 months for 2 years. Testosterone undecanoate intramuscular injection (1000 mg/4 mL) was supplied by Bayer (Reandron®) which is marketed in most countries as Nebido®.
The study found testosterone treatment for two years combined with a lifestyle program significantly reduced the prevalence of participants with T2D compared to lifestyle intervention only, in men with low testosterone levels.
*T2D for outcomes was defined as glucose ≥11.1 mmol/L, measured through a 2-hour oral glucose tolerance test.
Of the secondary endpoints, testosterone was associated with a benefit in body composition with a mean decrease in total fat mass of 2.7kg and a mean increase in total muscle mass of 1.7kg; both were statistically significantly greater than placebo. The safety profile was consistent with the label and with that seen in previous studies,1,2,8,9 The safety profile of the study was reassuring, with 41 serious adverse events recorded in the placebo group and 55 in the testosterone group, and no difference in incident cardiovascular events or prostate cancer.1 The data from this study provide some reassurance regarding 2-year cardiovascular safety and are in accordance with a recent meta-analysis indicating the cardiovascular safety of testosterone treatment.12 A treatment-limiting increase in haematocrit to 54% or higher, a prespecified safety trigger, was flagged in 106 (22%) of 491 participants treated with testosterone.1 This proportion is within the range of treatment-limiting increases in haematocrit (2.5 – 40%) in other studies of testosterone treatment.10,11 This trigger led to the cessation of treatment for 26 participants (25 in the testosterone group).1
Read the T4DM study report: Testosterone therapy for prevention and reversal of type 2 diabetes in men with low testosterone