Effect of Testosterone Treatment on Glucose Metabolism in Men With Type 2 Diabetes: A Randomized Controlled Trial

• Published in: Diabetes care Vol. 37; no. 8; pp. 2098 - 2107
• Main Authors: Gianatti, Emily J., Dupuis, Philippe, Hoermann, Rudolf, Strauss, Boyd J., Wentworth, John M., Zajac, Jeffrey D., Grossmann, Mathis
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2014
• Subjects: Abdominal Fat - metabolism; Adult; Aged; Androgens - administration & dosage; Biological and medical sciences; Blood Glucose - metabolism; Carbohydrate Metabolism; Clinical outcomes; Clinical trials; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrine therapy; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemic Agents - administration & dosage; Injections, Intramuscular; Insulin Resistance - physiology; Male; Medical sciences; Mens health; Metabolic diseases; Metabolism; Middle Aged; Obesity - complications; Testosterone; Testosterone - administration & dosage; Testosterone - analogs & derivatives; Testosterone - metabolism; Endocrinopathy; Type 2 diabetes; Human; Androgen; Nutrition; Metabolic diseases; Male; Glucose; Metabolism; Randomized controlled trial; Testosterone; Randomization; Treatment; Clinical trial; Testicular hormone; Sex steroid hormone; Endocrinology
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc13-2845

To determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. We conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35-70 years with an HbA1c ≤8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of ≤12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA1c (secondary outcome). Testosterone therapy did not improve insulin resistance (mean adjusted difference [MAD] for HOMA-IR compared with placebo -0.08 [95% CI -0.31 to 0.47; P = 0.23]) or glycemic control (MAD HbA1c 0.36% [0.0-0.7]; P = 0.05), despite a decrease in fat mass (MAD -2.38 kg [-3.10 to -1.66]; P < 0.001) and an increase in lean mass (MAD 2.08 kg [1.52-2.64]; P < 0.001). Testosterone therapy reduced subcutaneous (MAD -320 cm(3) [-477 to -163]; P < 0.001) but not visceral abdominal adipose tissue (MAD 140 cm(3) [-89 to 369]; P = 0.90). Testosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D.