Testosterone Replacement in Hypogonadal Men With Type 2 Diabetes and/or Metabolic Syndrome (the TIMES2 Study)
- T. Hugh Jones, MD, FRCP1,2⇓,
- Stefan Arver, MD3,
- Hermann M. Behre, MD4,
- Jacques Buvat, MD5,
- Eric Meuleman, MD6,
- Ignacio Moncada, MD7,
- Antonio Martin Morales, MD8,
- Maurizio Volterrani, MD, FCCP9,
- Ann Yellowlees, CSTAT10,
- Julian D. Howell, MB, BS, FRCS, MFPM11,
- Kevin S. Channer, MD, FRCP12 and
- TIMES2 Investigators
- 1The Robert Hague Centre for Diabetes and Endocrinology, Barnsley Hospital, Barnsley, U.K.
- 2Department of Human Metabolism, School of Medicine and Biomedical Science, University of Sheffield, Sheffield, U.K.
- 3Center for Andrology and Sexual Medicine, Karolinska University Hospital and the Karolinska Institute, Stockholm, Sweden
- 4Center for Reproductive Medicine and Andrology, University Hospital Halle (Saale), Martin-Luther University Halle-Wittenberg, Halle, Germany
- 5Centre d’Etudes et de Traitement de la Pathologie de l’Appareil Reproducteur et de la Psychosomatique (CETPARP), Lille, France
- 6Department of Urology, VU University Medical Center, Amsterdam, the Netherlands
- 7Department of Urology, Hospital Sanitas-La Zarzuela, Madrid, Spain
- 8Department of Urology, Carlos Haya University Hospital, Malaga, Spain
- 9Department of Cardiology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy
- 10Quantics Consulting Limited, Tweed Horizons, Newtown St Boswells, Scottish Borders, U.K.
- 11Clinical Research Department, ProStrakan, Galashiels, U.K.
- 12Department of Cardiology, Royal Hallamshire Hospital, Sheffield, U.K.
- ↵Corresponding author: T. Hugh Jones, .
OBJECTIVE This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS).
RESEARCH DESIGN AND METHODS The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12).
RESULTS TRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate.
CONCLUSIONS Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.
Clinical trial reg. no. ISRCTN457417, isrctn.org.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc10-1233/-/DC1.
- Received June 29, 2010.
- Accepted January 2, 2011.
- © 2011 by the American Diabetes Association.
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