T4DM study

The Lancet Diabetes & Endocrinology has published results from the T4DM (Testosterone for Diabetes Mellitus) a randomized, double-blind, placebo-controlled, phase 3b study, showing that testosterone treatment in men with low testosterone and diabetes or newly diagnosed diabetes for two years combined with lifestyle intervention significantly reduced type 2 diabetes (T2D) compared to placebo injection with lifestyle intervention in men with low testosterone levels.1

T4DM study

The Lancet Diabetes & Endocrinology has published results from the T4DM (Testosterone for Diabetes Mellitus) a randomized, double-blind, placebo-controlled, phase 3b study, showing that testosterone treatment in men with low testosterone and diabetes or newly diagnosed diabetes for two years combined with lifestyle intervention significantly reduced type 2 diabetes (T2D) compared to placebo injection with lifestyle intervention in men with low testosterone levels.1

T4DM chapters

    1 Introduction

    Introduction:

    You will hear opinions from a panel of experts on the world’s largest study of testosterone treatment, T4DM. With the help of hypogonadism experts and a patient many unanswered questions in this field will be addressed to acquire a better understanding of why change needs to happen.

    2 Effects of hypogonadism

    Effects of Hypogonadism:

    Discover the different symptoms linked to hypogonadism such as low energy drive, muscle weakness, depression and type 2 diabetes to name a few.

    3 Diagnosis of hypogonadism by general practitioners

    Diagnosis of Hypogonadism by General Practitioners:

    HCPs and Patients are looking to find the cause of these symptoms. Hear from GP Dr. Janine David about her experience in diagnosing hypogonadism, making a connection between erectile dysfunction, type 2 diabetes and low testosterone levels.

    4 Intro to T4DM study

    Intro to T4DM study:

    Find out why the T4DM study is portrayed as a landmark study, and receive valuable insights from Prof. Dr. Abraham Morgentaler.

    5 T4DM study and results

    T4DM Study and result:

    Listen to initial reactions and results from a panel of experts.

    6 Findings from the T4DM study and treatment of type 2 diabetes

    Findings from T4DM study and treatment of Type 2 Diabetes:

    Uncover how testosterone therapy can help short-term and long-term symptoms as well as reduce the risk of men developing type 2 diabetes.

    7 Clinical implication of T4DM study

    Global implication of T4DM study:

    Hear from a panel of experts what the clinical implication could be based on the study outcomes.

    8 Results of T4DM study impacting patients

    Results of T4DM study impacting patients:

    Explore how Nebido has been a major advancement in the treatment of men who have low levels of testosterone.

    9 Patients´ experiences on testosterone therapy

    Patient experiences on testosterone therapy:

    Hear a patient’s story on how the Nebido testosterone therapy changed there way of life.

    10 Early treatment of hypogonadism and future of testosterone therapy

    Early treatment of Hypogonadism and future of testosterone therapy:

    Learn how the T4DM study can help create change, earlier diagnosis and treatment of hypogonadism.

    Hypogonadism

    Hypogonadism is associated with several health consequences, such as cardiovascular disease, obesity, diabetes, osteoporosis, quality of life, and even economic impacts.

    Explaining the T4DM study

    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®.

    Key Findings

    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.

     

    The study met its two primary endpoints*

    1. 

    Reduction in T2D after two years

    • Testosterone treatment reduced T2DM compared to those in the placebo group after two years (12.4% (55/443) vs 21.1% (87/413) respectively), with a relative risk of 0.59 (95% CI: 0.43, 0.80; p=0.0007)

       

      A sub-group analysis showed that, after two years:

    • Of the men at high risk (pre-diabetes at baseline), 7.6% (27/355) of the testosterone group had progressed to T2D, compared with 14.9% (49/329) of the placebo group.
    • Of the men with newly-diagnosed T2D at baseline, 31.8% (28/88) of the testosterone group persisted with T2DM, compared with 45.2% (38/84) of the placebo group.
    2. 

    Mean change in 2-hour glucose from baseline after two years

    • There was a greater mean change from baseline in 2-hour glucose level in men treated with testosterone compared to placebo (-1.70 mmol/L vs -0.95 mmol/L respectively, with a mean difference of -0.75 mmol/L, p<0.0001/)

    *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