Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study).
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled trial
PubMed 21386088 · doi:10.2337/dc10-1233
What was done
A multicenter, prospective, randomized, double-blind, placebo-controlled trial (the TIMES2 study) evaluated the efficacy and safety of a transdermal 2% testosterone gel over 12 months in 220 hypogonadal men with type 2 diabetes, metabolic syndrome, or both. Phase 1 (months 0–6) prohibited background medication changes, while phase 2 (months 6–12) allowed medication adjustments. The primary outcome was mean change from baseline in HOMA-IR. Secondary outcomes included measures of body composition, glycemic control, lipids, and sexual function.
What was found
Testosterone replacement therapy reduced HOMA-IR across the overall study population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In patients with type 2 diabetes, HbA1c showed a significant treatment difference of -0.446% favoring testosterone at month 9 (P = 0.035). Improvements in total cholesterol, LDL cholesterol, lipoprotein(a), body composition, libido, and sexual function were reported in selected patient subgroups without exact numbers in the abstract. Adverse events and serious adverse events did not differ significantly between groups, with >95% categorized as mild or moderate.
Why it matters
This trial provides randomized evidence that transdermal testosterone replacement improves insulin resistance and glycemic control in hypogonadal men with type 2 diabetes or metabolic syndrome.
Limits
Numerical data and confidence intervals for secondary endpoints (lipids, body composition, sexual function) are omitted in the abstract. Background medication changes allowed in months 6–12 may confound long-term metabolic findings. The sample size was modest (n = 220) and long-term hard cardiovascular endpoints were not assessed.
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