Can Testosterone Therapy Prevent Type 2 Diabetes? What the T4DM and TRAVERSE Trials Found in Men With Prediabetes

Testosterone therapy has been tested twice as a way to stop prediabetes from becoming type 2 diabetes. The Australian T4DM trial found fewer new diabetes cases when testosterone injections were added to a lifestyle programme. The American TRAVERSE substudy, using testosterone gel without a structured lifestyle programme, found no significant difference.

Testosterone therapy can lower the chance that prediabetes becomes type 2 diabetes in some settings, but the evidence is split, and testosterone alone has not been shown to work. The T4DM trial, published by Gary Wittert and colleagues in Lancet Diabetes and Endocrinology in 2021, found that men given testosterone injections on top of a lifestyle programme were less likely to have diabetes after 2 years. The TRAVERSE substudy, published by Shalender Bhasin and colleagues in JAMA Internal Medicine in 2024, gave testosterone gel to men with low testosterone and prediabetes and found no significant reduction in progression to diabetes.

Men with low testosterone do develop diabetes more often. A 2025 meta-analysis in Endocrine by Vásquez-Tirado and colleagues pooled 22 longitudinal studies covering 43,038 men and found that low total testosterone was associated with higher odds of newly diagnosed type 2 diabetes, with an odds ratio of 1.52. An association is not proof that raising testosterone fixes the problem, which is exactly the question the two trials were built to answer.

Prediabetes is a blood sugar level that is above normal but below the threshold for diagnosing type 2 diabetes. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which uses American Diabetes Association cut-offs, prediabetes means an A1C of 5.7% to 6.4%, a fasting plasma glucose of 100 to 125 mg/dL, or a 2-hour oral glucose tolerance test result of 140 to 199 mg/dL.

The three tests do not always agree, and that disagreement turns out to matter for testosterone. The A1C test measures how much glucose has attached to haemoglobin inside red blood cells and reflects average blood sugar over roughly the past 3 months. The oral glucose tolerance test measures how well the body clears a sugar load in real time. A man can be in the prediabetes range on one test and normal on another.

The T4DM trial found that adding testosterone injections to a lifestyle programme reduced the proportion of men with type 2 diabetes after 2 years from 21% to 12%. T4DM, short for Testosterone for the Prevention of Type 2 Diabetes, ran at six Australian tertiary centres. Researchers pre-screened 19 022 men and randomised 1007 of them, about 5%, to testosterone (n=504) or placebo (n=503).

The T4DM men were aged 50 to 74, had a waist circumference of 95 cm or more and a serum testosterone of 14.0 nmol/L or lower, but did not have pathological hypogonadism. Every man had either impaired glucose tolerance, meaning a 2-hour glucose of 7.8 to 11.0 mmol/L, or newly diagnosed type 2 diabetes. All of them joined a community-based lifestyle programme, and WW (formerly Weight Watchers) was among the trial's funders. The testosterone group received intramuscular testosterone undecanoate 1000 mg at baseline, at 6 weeks, and then every 3 months.

The T4DM result was statistically strong. The relative risk of diabetes on testosterone was 0.59, with a 95% confidence interval of 0.43 to 0.80. Mean 2-hour glucose fell by 0.95 mmol/L in the placebo group and by 1.70 mmol/L in the testosterone group, a difference of 0.75 mmol/L. The treatment effect did not depend on how low a man's testosterone was at the start, which suggests that T4DM was not simply correcting a deficiency.

The T4DM investigators also reported that testosterone did not change HbA1c, even though it lowered glucose on the tolerance test and fasting glucose. In a 2023 review in the Journal of Endocrinology, Wittert, Grossmann, Yeap and Handelsman describe HbA1c as a red blood cell-dependent measure of glycaemic control, and they reported favourable changes in body composition, hand grip strength and bone in the testosterone group.

The TRAVERSE diabetes substudy found that testosterone gel did not significantly reduce progression from prediabetes to diabetes in men with low testosterone. TRAVERSE was a large American cardiovascular safety trial that enrolled men aged 45 to 80 with symptoms of hypogonadism, two fasting testosterone levels below 300 ng/dL, and existing or high-risk cardiovascular disease. The men applied 1.62% testosterone gel or a placebo gel daily, with the dose adjusted to keep testosterone between 350 and 750 ng/dL.

Of 5204 randomised TRAVERSE participants, 1175 had prediabetes and 3880 had diabetes. The men with prediabetes had a mean age of 63.8 and a mean HbA1c of 5.8%. Progression to diabetes ran a little lower on testosterone at every time point, but the gap was never statistically significant across the trial (omnibus P = .49). Among men who already had diabetes, testosterone did not increase the rate of glycaemic remission or improve glucose or HbA1c.

The chart above plots the percentages reported in the TRAVERSE substudy abstract. At 24 months, 10.1% of the testosterone group had progressed compared with 14.6% on placebo, and at 48 months the figures were 13.4% and 15.7%. The number of men still being measured shrank over time, which widens the uncertainty at the later points. The authors concluded that testosterone replacement alone should not be used to prevent or treat diabetes in men with hypogonadism.

T4DM and TRAVERSE tested different men, different drugs, different background care and different outcomes, so their results do not directly contradict each other. Neither trial was designed to explain the other, so any account of the gap is an interpretation. The differences below are the ones that stand out from the published designs.

The lifestyle programme is the most practical difference. Every T4DM man was already working to lose weight, and testosterone may have amplified that effort through the changes in body composition and grip strength the investigators reported. TRAVERSE tested testosterone in men who were not placed in a structured programme, which is closer to how testosterone is often prescribed in practice.

The choice of measurement may also matter. T4DM defined diabetes by the oral glucose tolerance test, and its investigators found no change in HbA1c. NIDDK notes that A1C results can be affected by anything that changes the life span of red blood cells, and testosterone raises red cell production, as the haematocrit numbers below show. Whether that explains any part of the TRAVERSE result has not been tested, so this is a reason to read HbA1c with care in men on testosterone rather than an established finding.

The main risk T4DM identified was a rise in haematocrit, which the investigators said might be treatment-limiting. A safety trigger for haematocrit above 54% occurred in 106 of 491 men (22%) on testosterone and 6 of 484 men (1%) on placebo. A trigger for a PSA rise of 0.75 ng/mL or more occurred in 23% of the testosterone group and 19% of the placebo group. Prespecified serious adverse events occurred in 10.9% of men on testosterone and 7.4% on placebo.

On heart safety, the main TRAVERSE trial of 5246 men, published by Michael Lincoff and colleagues in the New England Journal of Medicine in 2023, found that testosterone gel was non-inferior to placebo for major adverse cardiac events: 7.0% versus 7.3%, with a hazard ratio of 0.96. TRAVERSE also recorded more atrial fibrillation, acute kidney injury and pulmonary embolism in the testosterone group, so the heart result is reassuring about heart attacks and strokes rather than a blanket safety clearance.

The T4DM benefit did not appear to last after testosterone was stopped, based on a follow-up survey. David Handelsman and colleagues reported in the Journal of Clinical Endocrinology and Metabolism in 2023 that 599 T4DM men (59%) answered a survey a median of 5.1 years after their last injection. There was no difference between the former testosterone and placebo groups in self-reported new diagnoses of diabetes, prostate disease or cardiovascular disease.

The same follow-up found that former testosterone-group men were more likely to resume prescribed testosterone after the study (6% versus 2.8%), which the authors described as consistent with androgen dependence in some men. A new sleep apnoea diagnosis was also more common on testosterone during the trial (3.0% versus 0.4%). The follow-up relied on self-report from just over half the original men, so it is weaker evidence than the trial itself.

Lifestyle change remains the best-proven way to prevent type 2 diabetes. The Diabetes Prevention Program, published by William Knowler and colleagues in the New England Journal of Medicine in 2002, randomised 3234 people with raised glucose to placebo, metformin 850 mg twice daily, or a lifestyle programme aiming for at least 7 percent weight loss and at least 150 minutes of physical activity per week. Over an average of 2.8 years, the lifestyle programme reduced diabetes incidence by 58 percent and metformin by 31 percent compared with placebo.

The Diabetes Prevention Program population differs from T4DM: 68 percent were women and the mean age was 51 years, so its numbers should not be compared head to head with either testosterone trial. What the Diabetes Prevention Program does show is the size of the effect lifestyle change can produce on its own. T4DM is best read as evidence that testosterone added something on top of that foundation in a specific group of men, not as a replacement for it.

This article is for educational purposes only and is not medical advice. Nothing here diagnoses, treats, cures or prevents any disease, including type 2 diabetes, prediabetes or hypogonadism. Testosterone therapy and metformin are prescription treatments discussed only in terms of what published trials reported, and no one should start, stop or change a medication on the basis of this article. Speak with a licensed physician about your blood tests and medical history before making any decision.

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