TY - JOUR
T1 - Effect of Testosterone Treatment on Type 2 Diabetes Incidence in High-Risk Men Enrolled in a Lifestyle Program: A Two-Year Randomized Placebo-Controlled Trial
AU - Wittert, Gary A.
AU - Robledo, Kristy P.
AU - Grossmann, Mathis
AU - Bracken, Karen
AU - Yeap, Bu B.
AU - Stuckey, Bronwyn G. A.
AU - McLachlan, Robert I.
AU - Handelsman, David J.
AU - Allan, Carolyn
AU - Inder, Warrick
AU - Jesudason, David
AU - Keech, Anthony C.
AU - Jenkins, Alicia
AU - Fui, Mark Ng Tang
AU - Daniel, Mark
PY - 2020/6
Y1 - 2020/6
N2 - In men with obesity and IGT, serum testosterone (T) is inversely associated with incident T2D. Hypothesizing that T treatment prevents or reverses T2D beyond the effects of a lifestyle program alone, we conducted a multi-center, double-blinded placebo-controlled trial. Men (N=1007), aged 50-74 yrs., waist circumference (WC)>95cm, serum T≤14nmol/L (chemiluminescent assay), and IGT or newly diagnosed T2D, established by an OGTT, were randomized to receive, on a 1:1 basis, either IM T undecanoate (Reandron, Bayer) (1000mg/4ml) or vehicle (V) at baseline, 6 weeks and then 3-monthly for 2 yrs. All participants were enrolled in a lifestyle program (Weight Watchers® (WW)). Co-primary 2-yr outcomes: (1) OGTT 2-hr glucose ≥11 mmol/L: 55/443 (12.4%) in the T and 87/413 (21.1%) in V groups; RR (95% CI) 0.59 (0.43-0.80), P<0.001; and (2) mean change from baseline in 2-hr glucose: -1.70 mmol/L and -0.95 mmol/L in the T and V groups, respectively (mean difference -0.75 (95% CI -1.10 to -0.40) P<0.001). The treatment effect was independent of baseline serum T. Secondary 2-year outcomes: Greater decreases from baseline in fasting glucose by 0.17 mmol/L, WC by 2.1 cm, total fat mass by 2.7kg, and abdominal fat mass by 2.3%, and greater increases in total muscle mass by 1.7kg, arm muscle mass by 0.36kg and hand grip strength by 2.2kg, occurred in the T vs. V group (all P<0.004). Compliance with the WW program was similar in the T (30%) vs. V (28%) groups (P=0.89). Safety: Hematocrit ≥ 0.54: 106/491 (21.6%) vs. 6/484 (1.2%) in the T vs. V groups (P<0.001). SAEs in T vs. V groups (total events 55 vs. 42): Arrythmias (8 vs. 3), IHD (7 vs. 13), cerebrovascular disease (4 vs. 3), BPH (8 vs. 3), prostate cancer (4 vs. 5), other cancers (10 vs. 4), depression (1 vs. 3). There were 2 deaths in each group. Beyond a lifestyle program, T treatment reduced the RR of T2D by ∼40% at least partially mediated by favorable changes in body composition. Clinical Trial Registration: ACTRN12612000287831.
AB - In men with obesity and IGT, serum testosterone (T) is inversely associated with incident T2D. Hypothesizing that T treatment prevents or reverses T2D beyond the effects of a lifestyle program alone, we conducted a multi-center, double-blinded placebo-controlled trial. Men (N=1007), aged 50-74 yrs., waist circumference (WC)>95cm, serum T≤14nmol/L (chemiluminescent assay), and IGT or newly diagnosed T2D, established by an OGTT, were randomized to receive, on a 1:1 basis, either IM T undecanoate (Reandron, Bayer) (1000mg/4ml) or vehicle (V) at baseline, 6 weeks and then 3-monthly for 2 yrs. All participants were enrolled in a lifestyle program (Weight Watchers® (WW)). Co-primary 2-yr outcomes: (1) OGTT 2-hr glucose ≥11 mmol/L: 55/443 (12.4%) in the T and 87/413 (21.1%) in V groups; RR (95% CI) 0.59 (0.43-0.80), P<0.001; and (2) mean change from baseline in 2-hr glucose: -1.70 mmol/L and -0.95 mmol/L in the T and V groups, respectively (mean difference -0.75 (95% CI -1.10 to -0.40) P<0.001). The treatment effect was independent of baseline serum T. Secondary 2-year outcomes: Greater decreases from baseline in fasting glucose by 0.17 mmol/L, WC by 2.1 cm, total fat mass by 2.7kg, and abdominal fat mass by 2.3%, and greater increases in total muscle mass by 1.7kg, arm muscle mass by 0.36kg and hand grip strength by 2.2kg, occurred in the T vs. V group (all P<0.004). Compliance with the WW program was similar in the T (30%) vs. V (28%) groups (P=0.89). Safety: Hematocrit ≥ 0.54: 106/491 (21.6%) vs. 6/484 (1.2%) in the T vs. V groups (P<0.001). SAEs in T vs. V groups (total events 55 vs. 42): Arrythmias (8 vs. 3), IHD (7 vs. 13), cerebrovascular disease (4 vs. 3), BPH (8 vs. 3), prostate cancer (4 vs. 5), other cancers (10 vs. 4), depression (1 vs. 3). There were 2 deaths in each group. Beyond a lifestyle program, T treatment reduced the RR of T2D by ∼40% at least partially mediated by favorable changes in body composition. Clinical Trial Registration: ACTRN12612000287831.
U2 - 10.2337/db20-274-OR
DO - 10.2337/db20-274-OR
M3 - Meeting Abstract
SN - 0012-1797
VL - 69
SP - 1
EP - 1
JO - Diabetes
JF - Diabetes
ER -
