Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy

Aims: To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy. Materials and methods: We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels <7.3 nmol/L and T2D treated with metformin monotherapy. Patients were randomized to testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM), total and regional fat mass were measured using wholebody dual-energy X-ray absorptiometry scans. Whole-body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic-hyperinsulinaemic clamp with glucose tracer and combined with indirect calorimetry. Coefficients (beta) represent the placebo-controlled mean effect of intervention. Results: LBM (beta = 1.9 kg, p = 0.001) increased after TRT, while total fat mass (beta = -1.3 kg, p = 0.009), fat mass trunk (beta = -0.7 kg, p = 0.043), fat mass legs (beta = -0.7 kg, p = 0.025), fat mass arms (beta = -0.3 kg, p = 0.001), and HDL cholesterol (beta = -0.11 mmol/L, p = 0.009) decreased after TRT compared with placebo. Insulin-stimulated glucose disposal rates did not change in response to TRT compared with placebo (p = 0.18). Moreover, glycated haemoglobin, and basal and insulin-stimulated rates of EGP, lipid-and glucose-oxidation were unaltered after TRT. Conclusion: TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged.