Effect of testosterone on progression from prediabetes to diabetes in hypogonadal men

Low testosterone levels are associated with increased risk of prediabetes and type 2 diabetes in men. Experimental or therapeutic induction of testosterone deficiency in men is associated with increased fat mass, insulin resistance and type 2 diabetes. Furthermore, testosterone replacement therapy in men with hypogonadism has been shown to reduce whole body and visceral fat mass, increase muscle mass and improve insulin sensitivity. However, it is unknown whether testosterone replacement therapy in middle-aged or older men with hypogonadism affects the risk of progression from prediabetes to diabetes or induces glycemic remission in men with diabetes. To address this issue, the TRAVERSE Diabetes Study evaluated the efficacy of testosterone replacement therapy in preventing progression from prediabetes to diabetes in men with hypogonadism and prediabetes. The study also assessed whether testosterone replacement therapy was effective in inducing glycemic remission in men with diabetes.The trial was conducted at 316 sites in the United States. Participants included men aged 45–80 years with hypogonadism and prediabetes or diabetes. Participants were randomized 1:1 to receive testosterone 1.62% gel or placebo gel until study completion. The testosterone dose was titrated based on serum on-treatment testosterone levels and hematocrit to maintain serum on-treatment testosterone levels between 350–750 ng/dL (12–26 nmol/L). The primary end point was the risk of progression from prediabetes to diabetes (defined as A1C ≥ 6.5%, initiation of diabetes medication, or two consecutive fasting glucose level measurements > 125 mg/dL [> 6.9 mmol/L]). The secondary end point was the risk of glycemic remission (A1C < 6.5%) or two fasting glucose measurements < 126 mg/dL (< 7 mmol/L, without use of diabetes medication) in men who had diabetes.Results showed the following:The study included 5,204 randomized participants, 1,175 men with prediabetes (mean age, 63.8 years) and 3,880 men with diabetes (mean age, 63.2 years).Mean A1C in men with prediabetes was 5.8% (0.4%). Risk of progression from prediabetes to diabetes did not differ significantly between testosterone and placebo groups: 0.7% vs 1.4% at six months, 7.8% vs 10.7% at 12 months, 10.1% vs 14.6% at 24 months, 12.8% vs 15.8% at 36 months, and 13.4% vs 15.7% at 48 months. The proportion of participants with diabetes who experienced glycemic remission, as well as the changes in glucose and A1C levels, were similar in testosterone and placebo-treated men with prediabetes or diabetes.The authors comment that to their knowledge, the TRAVERSE Diabetes Study is the largest placebo-controlled randomized clinical trial to date to evaluate the efficacy of testosterone replacement therapy (without a lifestyle intervention) in preventing progression from prediabetes to diabetes in men with hypogonadism and in inducing glycemic remission in men with hypogonadism and diabetes. Based on their study results, the authors conclude that in men with hypogonadism and prediabetes, the incidence of progression from prediabetes to diabetes did not differ significantly between testosterone and placebo-treated men. In addition, testosterone replacement therapy did not improve glycemic control in men with hypogonadism and prediabetes or diabetes. These findings suggest that topical testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism.Reference1. Bhasin S, Lincoff AM, Nissen SE, et al. Effect of testosterone on progression from prediabetes to diabetes in men with hypogonadism. A substudy of the TRAVERSE randomized clinical trial. JAMA Intern Med 2024. Published online February 5, 2024. (accessed February 20, 2024).

Effect of testosterone on progression from prediabetes to diabetes in hypogonadal men

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