Remission of type 2 diabetes following long‐term treatment with injectable testosterone undecanoate in patients with hypogonadism and type 2 diabetes: 11‐year data from a real‐world registry study

Abstract

Aims: To investigate whether testosterone therapy (TTh) in men with hypogonadism and type 2 diabetes mellitus (T2DM) improves glycaemic control and insulin sensitivity, and results in remission of T2DM. Material and Methods: A total of 356 men who had total testosterone levels ≤12.1 nmol/L (350 ng/dL) and symptoms of hypogonadism were included in the study and followed up for 11 years. All patients received standard diabetes treatment and 178 patients additionally received parenteral testosterone undecanoate 1000 mg every 12 weeks following an initial 6-week interval. A control group comprised 178 hypogonadal patients who opted not to receive TTh. Results: Patients with hypogonadism and T2DM treated with testosterone had significant progressive and sustained reductions in fasting glucose, glycated haemoglobin (HbA1c) and fasting insulin over the treatment period. In the control group, fasting glucose, HbA1c and fasting insulin increased. Among the patients treated with testosterone 34.3% achieved remission of their diabetes and 46.6% of patients achieved normal glucose regulation. Of the testosterone-treated group, 83.1% reached the HbA1c target of 47.5 mmol/mol (6.5%) and 90% achieved the HbA1c target of 53.0 mmol/mol (7%). In contrast, no remission of diabetes or reductions in glucose or HbA1c levels were noted in the control group. There were fewer deaths, myocardial infarctions, strokes and diabetic complications in the testosterone-treated group. Conclusions: Long-term TTh in men with T2DM and hypogonadism improves glycaemic control and insulin resistance. Remission of diabetes occurred in one-third of the patients. TTh is potentially a novel additional therapy for men with T2DM and hypogonadism.

COVID-19, Type 2 Diabetes, and Hypogonadism: Lessons for Acute Management and Long-Term Prevention

“…As older men with T2DM are at greater risk of mortality from COVID-19, a therapy that potentially prevents progression to T2DM should also reduce the risk from COVID-19. 24,25 This approach is strongly endorsed by two recent review articles from Italy and the United States. 92,93 Current evidence-based guidelines from multiple medical disciplines already recommend screening, diagnosing, and treating men with hypogonadism in high-risk groups, such as type 2 diabetes, BMI >30 kg/m 2 , and men with ED.…”

“…23 Other articles have shown reversal of T2DM with TRT in a third of patients and reversal of prediabetes to normoglycemia compared with a control group. 24 A recent metaanalysis concluded that ''low testosterone levels in men with T2DM are associated with increased cardiovascular mortality'' and that ''testosterone therapy is associated with a reduction in all-cause mortality and cardiovascular events.'' 25 Recently a large multicenter randomized controlled trial (RCT) from Australia has been published.…”

“…In contrast, studies involving well-controlled patients, with minimal IR, showed mixed results, conclusions were consistent with a meta-analysis by Corona et al 29 (Table 1). 24,[30][31][32][33][34][35][36][37][38][39] Venous thrombotic embolism and testosterone Administration of exogenous testosterone can raise hematocrit values and potentially blood viscosity, along with platelet and thromboxane A2 concentrations, thereby enhancing the risk of venous thromboembolism. 40 Potentially this might increase risk in association with the severe endothelial dysfunction induced by COVID-19 infection.…”

Testosterone Therapy for Prevention and Treatment of Obesity in Men

“…26 Clinical Utility of TTh as a Treatment for Obesity: Long-Term RWE The RWE from long-term observational studies have provided compelling support for the use of TTh as a sustainable and feasible treatment for obesity. 42,[53][54][55][86][87][88][89][90][91][92][93] These observational studies comprise men with TD and various degrees of obesity and weight classes, ranging from normal weight to obesity class III, who are receiving long-term treatment with T undecanoate injections in real-life urology practices.…”

“…Another RWE analysis of 356 men with T2DM and TD examined whether long-term TTh can result in remission of T2DM. 92 Remission of T2DM was defined as HbA 1c <6.5% and discontinuation of all diabetes drugs, including metformin. All patients received standard T2DM treatment.…”