Testosterone Therapy Aids Type 2 Diabetes Remission

The male hormone reversed diabetes in a third of clinical trial participants

Testosterone to reduce hypogonadism

With Paresh Dandona MD, PhD and Elena Christofides MD

Long-term treatment with testosterone therapy in men with hypogonadism and type 2 diabetes improves their glycemic control as well as their insulin sensitivity, according to a new study. It can also lead to remission of diabetes in some. 

Low testosterone in men has been linked with an increased deposition of visceral fat, leading to higher insulin resistance and a risk of type 2 diabetes. Paresh Dandona MD, PhD, a SUNY distinguished professor at the University of Buffalo, co-authored the study. "The occurrence of this syndrome is common," he says. "With appropriate testosterone replacement, obesity, insulin resistance, and diabetes may be reversible."

Takeaways from previous research on testosterone and type 2 diabetes

In an earlier report published in 2004, Dr. Dandona and his colleagues pointed out the frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. "We started this field right here in 2004," Dr. Dandona tells Endocrine Web. In his experience, ''About one-third of men with type 2 diabetes have low testosterone at a level that would be called subnormal." 

In another previous study, published in 2016, Dr. Dandona demonstrated that men with type 2 diabetes and low testosterone levels can benefit significantly from hormone therapy. With the publication of that study, he described the results as ''The first definitive evidence that testosterone is an insulin sensitizer and hence a metabolic hormone."

The 2016 study evaluated 94 men, all with type 2 diabetes. Before being treated, the 44 men in the study with low testosterone expressed significantly lower levels of insulin signaling in adipose tissue, reflected in lower insulin sensitivity. These men were randomized to get a placebo or testosterone treatment weekly for 24 weeks. The researchers found a 32% increase in the uptake of glucose by tissues in response to insulin in the men treated with testosterone. Major genes mediating insulin signaling had increased expression.

Details of the new study on using testosterone to treat type patients with type 2 diabetes and hypogonadism

The current study was done at a urology practice in Germany over 11 years. 356 men were evaluated, and all received standard diabetes treatment which included mandatory educational courses and materials.

In addition, 178 men who were on average 62 years old received 1,000 milligrams of slow-release testosterone every 12 weeks after an initial 6-week interval. Another 178 men of a mean age of 64 opted out of the testosterone therapy and served as controls. They opted out for a variety of reasons, but the most common was getting advice against taking the testosterone therapy by their general practitioners. Others thought hypogonadal symptoms were a normal part of aging, while others declined due to the cost of the medication.

One third, or 34.3%, of those in the testosterone group saw remission of their type 2 diabetes. Nearly half, or 46.6%, had normal glucose regulation with antidiabetic treatments. 83% reached their target A1C level of 6.5%. In all, 90% reached the target of 7% or better. The control arm had no remission or reductions in glucose or A1C levels. The testosterone group also had fewer deaths, myocardial infarctions, strokes, and diabetic complications.

Among the limitations: The study was not a randomized clinical trial. Factors of the two groups were not balanced at baseline. Dr. Dandona believes the reversal of hyperglycemia and diabetes with testosterone treatment has not been shown previously. He calls for randomized controlled trials to confirm the value of the treatment and says one is now underway.

Other studies on using testosterone to prevent type 2 diabetes in men with hypogonadism

Other researchers have looked at testosterone treatment to prevent type 2 diabetes. In one study published in 2019, researchers from the University of Alabama at Birmingham and other institutions found that testosterone therapy in men with hypogonadism who were diagnosed with prediabetes (A1C of 5.7 to 6.4%) could keep them from developing diabetes. While 229 men received testosterone undecanoate, 87 were controls and not treated. A1C decreased by 0.39 in the treated group, while it increased by 0.63 in the untreated. Of those getting testosterone, 90% achieved normal glucose regulation, with an A1C of less than 5.7%.

The researchers noted significant improvements in fasting glucose, triglyceride to HDL ratio, total cholesterol, and other factors. Those treated with testosterone had fewer myocardial infarctions, too. While 0.4% of the treated group had an MI, 5.7% of the untreated did (P<0.005).

A second opinion on testosterone and type 2 diabetes remission

The changes Dr. Dandona found in his most recent study are not actually a full remission, says Elena Christofides MD, FACE, an endocrinologist in Columbus, Ohio, and a member of the editorial board of Endocrine Web. Once diagnosed with diabetes, she says, ''The genes you turned on have been turned on."

Right now, she believes, "It's currently out of favor to use testosterone in these patients. "However, the new study confirms what we have already known and seen in the past."

Current guidelines on testosterone therapy for diabetics

Guidelines issued by the Endocrine Society in 2018 recommend reserving testosterone therapy for well-documented cases of hypogonadism. Differences between the 2018 guidelines and the 2010 guidelines they replace include more rigorous appraisal of testosterone's efficacy and safety by relying on RCTs published during the last three years. The guidelines also point out continuing uncertainty about the benefits and risks of testosterone therapy as well as suboptimal testosterone prescribing practices. In all cases, an appropriate diagnostic work up and monitoring plan are crucial.

Takeaways for clinicians

As for the clinical significance, Dr. Dandona notes, ''One-third of men with type 2 diabetes have hypogonadism." For that reason, physicians do encounter men with both conditions very frequently, he says. 

Dr. Dandona has no disclosures relevant to the current study. Other authors report speaker honoraria from Bayer AG, which makes undecanoate. Dr. Christofides reports consultant work for Novo Nordisk, Eli Lilly, and Chiasma, and is on the speakers' bureau for Pfizer, Novo Nordisk, Eli Lilly, Boehringer Ingelheim, PamLab, and Shire.

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