Testosterone therapy associated with type 2 diabetes remission in men with hypogonadism
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One-third of a cohort of men with type 2 diabetes and hypogonadism who received testosterone undecanoate therapy experienced a sustained remission of their diabetes, according to findings from a single-center study.
“After we demonstrated the presence of hypogonadotropic hypogonadism in 33% of men with type 2 diabetes and among 25% of men without diabetes but with obesity, our colleagues in Bremerhaven, Germany, set up a registry for hypogonadal diabetics,” Paresh Dandona, MD, PhD, an Endocrine Today Editorial Board Member, SUNY distinguished professor and chief of endocrinology in the department of medicine at the University of Buffalo, New York, told Healio. “Our demonstration that testosterone is an insulin sensitizer led them to investigate the level of improvement in glycemic control among their patients. The control not only improved over 11 years of follow-up, but one-third of patients reversed their diabetes altogether.”
In a prospective, registry-based study published in Diabetes, Obesity and Metabolism, Karim Sultan Haider, MD, and Ahmad Haider, MD, both urologists in private practice in Bremerhaven, Germany, Farid Saad, DVM, PhD, senior consultant for Bayer AG, Medical Affairs Men’s Health, in Hamburg, Germany, and professor in the research department of Gulf Medical University in Ajman, United Arab Emirates, Dandona and colleagues analyzed data from 356 men with type 2 diabetes, a total testosterone level of 12.1 nmol/L or lower and symptoms of hypogonadism, all examined in a single urological practice for 11 years. All men received standard diabetes treatment and were enrolled into a mandatory disease management education program for diabetes. Within the cohort, 178 men received 1,000 mg parenteral testosterone undecanoate every 12 weeks after an initial 6-week interval (mean age, 62 years; mean follow-up, 7.7 years) and 178 men who declined testosterone therapy served as controls (mean age, 64 years; mean follow-up, 8.7 years). Five men in the testosterone group and six men in the control group had primary hypogonadism (one with Klinefelter syndrome).
“Most of the patients had hypogonadotropic hypogonadism, consistent with their type 2 diabetes,” the researchers wrote.
At least twice yearly, researchers measured fasting glucose, HbA1c, insulin, blood pressure, lipid profile and total testosterone, as well as quality of life using the Aging Males’ Symptoms scale and erectile dysfunction using the International Index of Erectile Function. Researchers used a mixed-effects model to compare mean changes over time between men who received testosterone and controls.
Researchers found that men with hypogonadism and type 2 diabetes treated with testosterone experienced “significant progressive and sustained” reductions in fasting glucose, HbA1c and fasting insulin during the treatment period. Among controls, fasting glucose, HbA1c and fasting insulin increased. Among men who received testosterone therapy, 34.3% experienced diabetes remission, defined as an HbA1c of 6.5% or lower and discontinuation of all diabetes medications, and 46.6% of men achieved normal glucose regulation. The average time to discontinuation of diabetes medications was 8.6 years. Most men (83.1%) in the testosterone group reached an HbA1c target of 6.5% and 90% achieved an HbA1c target of 7%.
“We observed a significant reduction in HbA1c exceeding 3 percentage points in men with hypogonadism and type 2 diabetes treated with testosterone, even after adjustments for baseline variables,” the researchers wrote. “These reductions in HbA1c were sustained throughout the treatment period.”
There was no remission of diabetes or reduction in glucose or HbA1c levels among controls, according to the researchers.
The researchers also observed fewer deaths, myocardial infarctions, strokes and diabetes complications in the testosterone group.
“Clearly, the reversal of diabetes was unexpected and to the uninitiated, it would sound like science fiction,” Dandona said. “The message is clear. All people with type 2 diabetes and/or obesity should have their testosterone measured and, if appropriate, be treated with testosterone for hypogonadism.”
For more information:
Paresh Dandona, MD, PhD, can be reached at the Jacobs School of Medicine and Biomedical Sciences, the University of Buffalo, 1020 Youngs Road, Williamsville, NY 14221; email: dandona@buffalo.edu.
Perspective
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Abraham Morgentaler, MD, FACS
How incredible that testosterone therapy could achieve remission of type 2 diabetes among a third of individuals in this cohort. Skeptics will correctly point out this is a single-center study that requires confirmation; however, it is important to note that this result is a logical extension of known effects of testosterone therapy in testosterone-deficient men, namely, loss of fat mass and increased lean mass. This is one more potential example of the general health benefits of testosterone therapy in affected individuals.
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