The headline result
Testosterone injections, added to a structured lifestyle program, lowered the share of men who had diabetes-range glucose after two years. In the T4DM trial, published in 2021 in The Lancet Diabetes and Endocrinology, 12% of men on testosterone met the diabetes threshold at two years, compared with 21% of men on placebo, a relative risk of 0.59.
That is a striking number, and it is easy to over-read. The men in T4DM did not have the kind of low testosterone that testosterone products are approved to treat, the benefit came with a large jump in red blood cell counts, and a later analysis from a different trial did not find the same protection. All three points matter before anyone treats testosterone as a diabetes drug.
How was T4DM designed?
T4DM tested whether testosterone could prevent or reverse early type 2 diabetes beyond what lifestyle change achieves. Six Australian hospital centers pre-screened 19,022 men and enrolled 1,007. To qualify, men had to be 50 to 74 years old, have a waist of 95 cm or more, and have either impaired glucose tolerance or newly diagnosed type 2 diabetes on an oral glucose tolerance test.
Testosterone had to be 14.0 nmol/L or lower, which is roughly 400 ng/dL, but men with pathological hypogonadism were excluded. In other words, these were men with low-normal levels linked to age and weight, not men with failing testes or pituitary disease.
Every participant joined a community-based lifestyle program. On top of that, men received an injection of testosterone undecanoate 1,000 mg or placebo at the start, at six weeks and then every three months for two years. Funding came from Australia’s National Health and Medical Research Council along with Bayer, Eli Lilly, the University of Adelaide and WW (formerly Weight Watchers).
What did the trial find?
The main outcome was a two-hour glucose of 11.1 mmol/L or higher on the glucose tolerance test, which corresponds to the 200 mg/dL diabetes cutoff the NIDDK uses for that test. Here is how the groups compared at two years:
| Outcome at two years | Testosterone | Placebo |
|---|---|---|
| Diabetes-range glucose tolerance test | 12% (55 of 443) | 21% (87 of 413) |
| Average change in two-hour glucose | Down 1.70 mmol/L | Down 0.95 mmol/L |
| Hematocrit safety trigger above 54% | 22% (106 of 491) | 1% (6 of 484) |
| PSA rise of 0.75 or more | 23% | 19% |
| Prespecified serious adverse events | 10.9% | 7.4% |
Two details stand out. The benefit did not depend on how low a man’s testosterone was at the start, and both groups improved, because the lifestyle program helped everyone. Testosterone added to that improvement rather than replacing it.
The safety row is the one clinicians notice first. More than one in five men on testosterone crossed the hematocrit trigger, and the authors wrote that rising hematocrit might limit treatment. They also said longer-term durability, safety and cardiovascular effects still needed study.
Why is this not an approved use of TRT?
Testosterone products are approved for a specific job. The FDA’s testosterone information page says they are approved only for men who lack testosterone or have low levels in conjunction with an associated medical condition, such as testicular failure or a hypothalamus or pituitary problem. Preventing diabetes is not on that list, and T4DM deliberately enrolled men without pathological hypogonadism. The same FDA page notes that in June 2026 the agency asked for label updates, including removal of the limitation about age-related low testosterone, and none of those updates added a diabetes use.
A single trial, however well run, also does not make a new indication. Regulators would expect confirmation, longer follow-up and a clear picture of harms, and the hematocrit finding alone would shape how any such use was monitored.
What did TRAVERSE add?
A larger U.S. trial pointed the other way for testosterone used on its own. In a TRAVERSE substudy published in 2024, 1,175 men with hypogonadism and prediabetes received testosterone gel or placebo. Progression to diabetes did not differ significantly between groups; at 24 months it was 10.1% on testosterone and 14.6% on placebo, with an overall test across time points that was not significant. Among 3,880 men who already had diabetes, testosterone did not raise remission rates or improve A1c.
The TRAVERSE authors concluded that testosterone alone should not be used to prevent or treat diabetes in men with hypogonadism. The two trials differ in drug, route and, most importantly, in whether a structured lifestyle program came with the treatment. The fair reading is that any glucose benefit from testosterone, if real, appears alongside serious lifestyle change, not instead of it.
What it means for men with prediabetes
If your A1c or fasting glucose is creeping up, the reliable levers are still weight loss, activity and, when appropriate, medicines designed for metabolism. The Endocrine Society’s 2026 statement says that when low testosterone is due to overweight or obesity with no other cause, weight loss is typically the first-line therapy. Our page for men with prediabetes lays out that plan.
Testosterone still has a place when it is genuinely needed. A man with confirmed low levels on repeat morning tests and symptoms that fit may be treated for that diagnosis, and better glucose control can be a welcome side benefit rather than the reason. If that happens, hematocrit deserves close attention, as our article on high hematocrit on TRT explains. Our answer on whether TRT can reverse prediabetes covers the question in short form.
How Ultimate Male approaches blood sugar and testosterone
At our San Gabriel and Downey clinics, the first step is measurement: A1c, fasting glucose and a testosterone workup, drawn on site with results usually in 24 to 48 hours. Our HbA1c test for men page explains what the number shows. A PA-C or MD then separates the two questions, whether your blood sugar needs a plan and whether your testosterone is truly low.
For blood sugar and weight, that often means medical weight loss with labs, body composition analysis and regular check-ins. For confirmed hypogonadism, it may mean testosterone therapy with the monitoring T4DM showed is needed. The free 10-minute call is where to start sorting out which applies to you.
