The effect of testosterone treatment on glucose metabolism and other health outcomes in men with type 2 diabetes: a randomized controlled trial

© 2016 Dr. Emily Jaye GianattiContext: The efficacy and safety of testosterone treatment in men with type 2 diabetes mellitus (T2D) and low to low-normal circulating testosterone levels is unknown. The number of testosterone prescriptions has increased significantly throughout the developed world whilst the prevalence of traditional indications for treatment is unchanged. This in part reflects increased prescription for novel indications such as T2D in the absence of sufficient efficacy and safety data. The effects of testosterone treatment on insulin resistance and other health outcomes in men with T2D were studied using rigorous methodology in this randomized controlled trial (RCT). Objective and Patients: In this 40-week RCT of 88 men with T2D, we investigated the effect of intramuscular testosterone undecanoate on insulin resistance as measured by homeostasis model assessment of insulin resistance (HOMA2-IR). Effects on glycemic control, body composition, sexual and constitutional symptoms and cardiac biomarkers were also assessed. Results: Testosterone treatment did not improve insulin resistance (Mean adjusted difference (MAD) for HOMA2-IR compared with placebo over 40 weeks -0.08 [95% CI -0.31 to 0.47] p=0.23) or glycemic control (MAD HbAlc 0.36% [0.0,0.7] p=0.05) despite a decrease in fat mass (MAD -2.38kg [-3.10,-1.66] p<0.001) and an increase in lean mass (MAD 2.08kg [1.52, 2.64] p<0.001). Testosterone treatment reduced subcutaneous abdominal adipose tissue volume (MAD SAT -320 cm3 [-477,-163] p<0.001) but not visceral abdominal adipose tissue volume (MAD VAT 140cm3 [-89,369] p=0.90) and did not increase adiponectin levels (MAD -3.3 ug/ml [-8.2,1.6] p=0.42). Testosterone treatment did not improve constitutional symptoms as measured by Aging Male Symptom (AMS) score (MAD AMS -0.9 [-4.1,2.2] p=0.67) but reduced erectile function as measured by International Index of Erectile Function abridged version 5 (IIEF-5) (MAD IIEF-5 -2.0 [-3.4,-0.6] p<0.02). No significant difference between baseline and 40 week IIEF-5 scores were noted when both groups were analyzed separately. At baseline symptoms were worse in men with depression (AMS 39 vs. 31 p=0.002, IIEF-5 17 vs. 18 p=0.53) and microvascular complications (Neuropathy AMS 38 vs. 32 p=0.04, IIEF-5 8 vs. 18 p=0.03, Retinopathy AMS 40 vs. 33 p=0.22, IIEF-5 7 vs. 18 p=0.02) but did not correlate with testosterone levels (Total testosterone AMS -0.02 p=0.78, IIEF-5 0.09, p=0.37). Testosterone treatment reduced N terminal pro brain natriuretic peptide (NT-proBNP) levels (MAD -17.9 ng/L [-32.4,-3.5] p=0.047) but did not change high sensitivity cardiac troponin T (hs cTnT) levels (MAD 0.41ng/L [-0.56,1.39] p=0.62). Six men, three in each group experienced an adverse cardiac event, displaying already higher baseline NT-proBNP (p