Effect of Testosterone on Progression From Prediabetes to Diabetes in Men With Hypogonadism: A Substudy of the TRAVERSE Randomized Clinical Trial.

Risk of progression from prediabetes to diabetes did not differ significantly between testosterone and placebo groups across all time points.

• Progression rates at 6 months: 4 of 598 (0.7%) in testosterone group vs 8 of 562 (1.4%) in placebo group
• Progression rates at 12 months: 45 of 575 (7.8%) vs 57 of 533 (10.7%)
• Progression rates at 24 months: 50 of 494 (10.1%) vs 67 of 460 (14.6%)
• Progression rates at 36 months: 46 of 359 (12.8%) vs 52 of 330 (15.8%)
• Omnibus test P = .49, indicating no statistically significant difference overall

Testosterone replacement therapy did not improve glycemic control in men with hypogonadism and prediabetes or diabetes.

• The proportions of participants with diabetes who experienced glycemic remission were similar in testosterone- and placebo-treated men
• Changes in fasting glucose levels were similar between treatment groups in both prediabetes and diabetes cohorts
• Changes in hemoglobin A1c levels were similar in testosterone- and placebo-treated men with prediabetes or diabetes
• Glycemic remission was defined as HbA1c level <6.5% or 2 fasting glucose measurements <126 mg/dL without diabetes medication

The study population included 1175 men with prediabetes and 3880 men with diabetes from a total of 5204 randomized TRAVERSE participants.

• Men with prediabetes had a mean (SD) age of 63.8 (8.1) years
• Men with diabetes had a mean (SD) age of 63.2 (7.8) years
• Mean (SD) hemoglobin A1c level in men with prediabetes was 5.8% (0.4%)
• Participants were enrolled between May 23, 2018, and February 1, 2022, at 316 trial sites in the US
• Participants were randomized 1:1 to receive 1.62% testosterone gel or placebo gel

The primary end point of risk of progression from prediabetes to diabetes was analyzed using repeated-measures log-binomial regression in an intention-to-treat framework.

• The study was a nested substudy within the TRAVERSE placebo-controlled randomized clinical trial (ClinicalTrials.gov Identifier: NCT03518034)
• The secondary end point was the risk of glycemic remission in men who had diabetes
• Participants were men aged 45 to 80 years with hypogonadism and either prediabetes or diabetes

Based on these findings, TRT alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism.

• Neither prevention of diabetes progression nor induction of glycemic remission was demonstrated with TRT
• The lack of effect was observed across multiple time points from 6 to 48 months
• At 48 months, progression rates were 13.4% in the testosterone group vs 15.7% in the placebo group, still not significantly different