Research presented at ENDO 2026 by Gary Wittert, MBBch, MD, examined whether testosterone treatment can replace lifestyle intervention in older men with central obesity who have prediabetes or early type 2 diabetes. The analysis reinforces that testosterone may produce metabolic and body-composition benefits but is not a stand-alone substitute for diet, exercise, or structured weight-management programs.
Type 2 diabetes prevalence is high, particularly in adults aged 45 and older. The condition is closely linked to abdominal obesity and loss of muscle mass and strength. Early detection and intervention can reduce the risk of downstream complications, and lifestyle programs remain a cornerstone of diabetes prevention.
The findings reported at ENDO 2026 are based on a sub-analysis of the Testosterone for the Prevention of Type 2 Diabetes Mellitus (T4DM) trial, a randomized, double-blind, placebo-controlled study published in 2021. The parent trial enrolled 1,007 men aged 50–74 who were at high risk of developing or had newly diagnosed type 2 diabetes.
Within the T4DM trial, participants received either testosterone or placebo in combination with a lifestyle program. The original trial showed that testosterone plus lifestyle intervention reduced the likelihood of diabetes being present after two years.
This new research followed a subgroup of 121 men from the T4DM cohort who elected to continue blinded treatment for two additional years but did not remain enrolled in the lifestyle program. The extension aimed to determine longer-term effects of testosterone on blood glucose control, measures of obesity, skeletal muscle mass and strength, sexual function, and safety up to four years.
The subgroup design allowed investigators to observe which effects persisted when participants were no longer actively engaged in the structured lifestyle intervention that accompanied the initial trial period.
Results indicated that most of the benefits on blood sugar control occurred during the first two years of the trial. By the fourth year, much of the early improvement had diminished, although blood glucose control in the testosterone-treated group remained significantly better than in the placebo group at four years.
These findings suggest that while testosterone can contribute to improved glycemic measures initially, sustained metabolic benefit is closely tied to continued lifestyle engagement and weight-management efforts.
Improvements in body composition—including reductions in fat mass and increases in muscle mass—observed during the initial two years were maintained at the four-year mark. Similarly, gains in sexual desire that emerged early in treatment were preserved through the extended follow-up.
The maintenance of these changes despite discontinuation of the structured lifestyle program for the subgroup suggests some durable effects of testosterone on body composition and libido, though the magnitude and clinical relevance should be interpreted in the context of the study’s design and the subgroup’s characteristics.
Overall quality of life did not differ clearly between the testosterone and placebo groups at either two or four years; measures were similar across both arms throughout the four-year period.
No new safety concerns were identified during the extended follow-up of the subgroup. The report does not detail specific adverse-event rates or new safety signals beyond stating that no new concerns emerged in this population.
Lead author Gary Wittert emphasizes that “testosterone treatment alone is not a replacement for lifestyle intervention, weight management or standard diabetes prevention in older men with central obesity and prediabetes or early type 2 diabetes.” He highlights that ongoing participation in a structured weight-management program is critical for maintaining and maximizing the benefits of testosterone therapy.
Wittert also suggests clinicians should view men’s metabolic health, waist circumference, muscle health, sexual symptoms and testosterone status as interconnected issues rather than managing each domain in isolation. The extended sub-study reinforces the role of lifestyle programs in diabetes prevention and indicates that testosterone may augment—but not substitute for—those interventions.
Limitations and details not reported in the source: the extended sub-study size (121 participants) and the fact that these participants were not enrolled in the lifestyle program after year two are reported; specific numerical outcomes, effect sizes, statistical measures, and granular safety-event data were not provided in the source article.
In summary, the ENDO 2026 presentation of the T4DM sub-study supports the use of testosterone as an adjunct to lifestyle intervention for selected older men at metabolic risk, while underscoring that structured lifestyle change remains essential for durable diabetes prevention and metabolic control.