Meeting NewsPerspective

Long-term testosterone therapy may prompt type 2 diabetes remission in men

ORLANDO, Fla. — Among men with hypogonadism included in a urology registry, long-term treatment with testosterone may lead to remission of type 2 diabetes, according to a speaker.

“This registry was not designed to study the effects of testosterone on type 2 diabetes,” Farid Saad, PhD, of Bayer Pharma in Berlin, said during the presentation. “A remission of type 2 diabetes with testosterone has not been described in the literature. It was completely unexpected.”

Saad and colleagues evaluated data from 400 men included in a urology registry of patients with hypogonadism (testosterone ≤ 12.1 nmol/L) since 2004; 133 (33.3%) of them had been diagnosed with type 2 diabetes and were treated in a diabetes center. All men received injections of testosterone undecanoate 1,000 mg for 12 weeks for hypogonadism. At least twice a year, anthropometric and metabolic measurements were obtained, and fasting insulin was acquired from the diabetes center to calculate homeostasis model assessment for insulin resistance. Participants were followed for a mean of 6.9 years, with a maximum of 11 years. At baseline, mean age of the participants was 60 years.

The researchers found that at the final measurement, 16 men (12%) were in diabetes remission. They observed a reduction in HbA1c from 8.3% at baseline to 5.7%. Also decreased from baseline to last measurement were fasting glucose (from 7.8 mmol/L to 5.4 mmol/L) and fasting insulin (from 24.7 µU/mL to 7.6 µU/mL). HOMA-IR decreased from 8.7 to 1.8, and triglycerides dropped from 3.2 mmol/L to 2.2 mmol/L.


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decrease in body weight from baseline was observed, from 107 kg to 89 kg, and a reduction in waist circumference from 108 cm to 97 cm. At baseline, all participants had been prescribed oral metformin, and five were on a regimen of insulin at an average dose of 21.6 units per day. Patients were observed for an average of 106.3 months. Discontinuation of diabetes medication occurred at an average of 74.8 months. One patient discontinued testosterone after a diagnosis of low-grade prostate cancer and, subsequently, developed new-onset type 2 diabetes. This patient again experience diabetes remission 48 months after resuming testosterone therapy. Because all injections were given in the urology office, medication adherence was 100%.

Saad weighed the potential cardiovascular benefits of diabetes remission, weight loss and decreased lipid levels against assertions that testosterone treatment itself confers CV risk.

“We do have a control group that is hypogonadal that did not receive testosterone treatment, and we see that of the threefold increase in mortality in the untreated hypogonadal patients compared to the treated patients, this mortality is usually of a cardiovascular nature, which is not the case in the treated patients,” he said. “So, in our experience, everything that was said about cardiovascular risk increased by testosterone treatment is nonsense.” – by Jennifer Byrne

Reference:

Saad F, et al. 125-OR. Presented at: American Diabetes Association 78th Scientific Sessions; June 22-26, 2018; Orlando, Fla.

Disclosure: Saad reports he is an employee of Bayer AG and holds stock/shares in Bayer AG and Novo Nordisk.

ORLANDO, Fla. — Among men with hypogonadism included in a urology registry, long-term treatment with testosterone may lead to remission of type 2 diabetes, according to a speaker.

“This registry was not designed to study the effects of testosterone on type 2 diabetes,” Farid Saad, PhD, of Bayer Pharma in Berlin, said during the presentation. “A remission of type 2 diabetes with testosterone has not been described in the literature. It was completely unexpected.”

Saad and colleagues evaluated data from 400 men included in a urology registry of patients with hypogonadism (testosterone ≤ 12.1 nmol/L) since 2004; 133 (33.3%) of them had been diagnosed with type 2 diabetes and were treated in a diabetes center. All men received injections of testosterone undecanoate 1,000 mg for 12 weeks for hypogonadism. At least twice a year, anthropometric and metabolic measurements were obtained, and fasting insulin was acquired from the diabetes center to calculate homeostasis model assessment for insulin resistance. Participants were followed for a mean of 6.9 years, with a maximum of 11 years. At baseline, mean age of the participants was 60 years.

The researchers found that at the final measurement, 16 men (12%) were in diabetes remission. They observed a reduction in HbA1c from 8.3% at baseline to 5.7%. Also decreased from baseline to last measurement were fasting glucose (from 7.8 mmol/L to 5.4 mmol/L) and fasting insulin (from 24.7 µU/mL to 7.6 µU/mL). HOMA-IR decreased from 8.7 to 1.8, and triglycerides dropped from 3.2 mmol/L to 2.2 mmol/L.


A
decrease in body weight from baseline was observed, from 107 kg to 89 kg, and a reduction in waist circumference from 108 cm to 97 cm. At baseline, all participants had been prescribed oral metformin, and five were on a regimen of insulin at an average dose of 21.6 units per day. Patients were observed for an average of 106.3 months. Discontinuation of diabetes medication occurred at an average of 74.8 months. One patient discontinued testosterone after a diagnosis of low-grade prostate cancer and, subsequently, developed new-onset type 2 diabetes. This patient again experience diabetes remission 48 months after resuming testosterone therapy. Because all injections were given in the urology office, medication adherence was 100%.

Saad weighed the potential cardiovascular benefits of diabetes remission, weight loss and decreased lipid levels against assertions that testosterone treatment itself confers CV risk.

“We do have a control group that is hypogonadal that did not receive testosterone treatment, and we see that of the threefold increase in mortality in the untreated hypogonadal patients compared to the treated patients, this mortality is usually of a cardiovascular nature, which is not the case in the treated patients,” he said. “So, in our experience, everything that was said about cardiovascular risk increased by testosterone treatment is nonsense.” – by Jennifer Byrne

Reference:

Saad F, et al. 125-OR. Presented at: American Diabetes Association 78th Scientific Sessions; June 22-26, 2018; Orlando, Fla.

Disclosure: Saad reports he is an employee of Bayer AG and holds stock/shares in Bayer AG and Novo Nordisk.

    Perspective
    Paresh Dandona

    Paresh Dandona

    We first described the syndrome of hypogonadotropic hypogonadism in type 2 diabetes in 2004, and since the only correlation was with BMI, we connected the syndrome to obesity (Dhindsa S, et al. J Clin Endocrinol Metab. 2004;doi:10.1210/jc.2004-0804). We know that 33% of type 2 diabetic males are hypogonadal, and 25% of nondiabetic obese men are hypogonadal. Then we looked at a population of 14- to 20-year-old males and discovered that simple obesity gives them testosterone levels half those of normal children — they will not become sexually mature. This is a major epidemic.

    The presentation by Saad and colleagues occurs in a setting where we have all of these data, but there are still a lot of disbelievers.

    Following our initial studies, Saad, along with urologists in Hamburg, then started treating these patients with testosterone. His work now has culminated in 8 to 10 years’ follow-up showing a lot of those patients kept on losing weight with testosterone, kept on lowering their blood pressure, and 12 out of those 36 went into diabetes remission.

    What is happening is probably circular. Obesity leads to the syndrome and to diabetes, but when you give testosterone, adiposity goes away along with the syndrome and the diabetes. My colleagues and I showed in a study published 2 years ago in Diabetes Care (2016;doi:10.2337/dc15-1518) that when we gave testosterone to these patients, they lost 3.5 kg of body weight in 6 months and added 3.5 kg of muscle. But not only that, their insulin resistance fell dramatically by 35%. A 35% reduction is almost as good as that seen with pioglitazone or insulin sensitizers. Saad’s study is the next step. Now, we should be looking at these patients with a vengeance, and if they need treatment, to treat them. A lot of them will have improvement in sexual function and that’s fine, but even if they don’t, they will see a metabolic benefit.

    • Paresh Dandona, MD, PhD
    • Endocrine Today Editorial Board Member SUNY Distinguished Professor Chief of Endocrinology Department of Medicine University of Buffalo, New York

    Disclosures: Dandona reports various financial ties with AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Novo Nordisk and Sanofi Aventis.

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