Evidence That Testosterone Could Lead to Remission of Type 2 Diabetes
Since at least 2004, the Special Warnings and Special Precautions section in the label of testosterone products states that “improved insulin sensitivity may occur in patients treated with androgens…” At that time, very few studies had investigated the relationship between testosterone and insulin sensitivity. As early as the 1990s, the group of Per Björntorp in Gothenburg, Sweden, found a positive correlation between visceral fat and 2‐hr glucose, 2‐hr insulin following an oral glucose tolerance test (OGTT) as well as fasting C‐peptide, but a negative correlation with testosterone. Hence, there has been “hidden” knowledge, but nobody could foresee what is known today about the effects of testosterone therapy (TTh) in men with type 2 diabetes (T2D).
Studies using TRT in men with testosterone deficiency (hypogonadism) and T2D show remarkable differences depending on their duration. To cite just a few examples, Heufelder et al. 2009 have shown that reduction of HbA1c was measurable after three months but continued to improve after 12 months, over and beyond the effects of a structured lifestyle intervention in men with newly diagnosed T2D. Hackett et al. 2014 saw little change in HbA1c during the initial six months, but a steep drop in the following 12 months. Groti et al. 2020 found a good effect of TRT in the first year of their study, and all effects further improved in the second year.
Many population‐based studies revealed a robust inverse correlation between lean body mass and insulin resistance. TRT invariably increases lean body mass. Independent controlled studies reported an increase in a magnitude up to 4.8 kg/year. This effect of TRT may be the single most important effect mediating the improvement of glycemic control.
In a long‐term registry, Haider et al. 2020 not only showed a profound reduction of HbA1c, fasting glucose, fasting insulin and HOMA‐IR in men with T2D receiving TRT, they also reported for the first time that more than a third of their patients achieved remission of T2D under long‐term TRT. Mean time to remission, defined as discontinuation of all diabetes drugs while maintaining stable HbA1c below 6.5%, was 8.6 years. Almost half of the patients achieved normal glucose regulation (HbA1c <5.7%). These results have led to the hypothesis that TRT may reverse the pathophysiology of T2D – poor lifestyle habits resulting in overeating and lack of physical activity, obesity, insulin resistance, prediabetes and finally T2D – as slowly as it develops. The group also showed a highly significant reduction of mortality, confirming previously published results in men with T2D receiving TRT.
In summary, substantial knowledge has accumulated over more than 30 years regarding the relationship between testosterone, testosterone therapy, and type 2 diabetes. Longer‐term trials and long‐term registries show profound benefits of testosterone therapy in men with hypogonadism and type 2 diabetes which may result in remission.
Farid Saad: Lecturer at Dresden International University, Dresden, Germany