July 05, 2018
After almost a decade of testosterone injections every 3 months, 22% of men with type 2 diabetes and hypogonadism had diabetes remission, in unexpected findings from a small registry study that was only designed to assess a new preparation of the hormone.
"In the total group of 133 patients, there was not a single patient who did not benefit from testosterone therapy," said Farid Saad, DVM, PhD, manager of Global Medical Affairs Andrology at Bayer, in Berlin, Germany.
And patients with the "longest treatment duration had the highest probability to go into remission," noted Saad, who presented the findings in an oral session here at the American Diabetes Association (ADA) 2018 Scientific Sessions and is also honorary professor at Gulf Medical University in Ajman, United Arab Emirates.
Moreover, "we almost see no weight loss in the first year," he elaborated. But then as time goes on, “weight comes down, the glycemic control gets better and better, and we see a normalization of the total situation."
Clinicians "should be aware of the high prevalence of hypogonadism (testosterone deficiency) in men with type 2 diabetes," Saad told Medscape Medical News.
Importantly, "testosterone therapy is not a 'quick fix' but will require years of [consistent therapy] and high adherence to achieve optimal results," but diabetes itself requires lifelong medical therapy.
These are "exciting, compelling" data, but we need to see these results replicated in a randomized controlled trial, cautioned session chair Tricia Santos Cavaiola, MD, an endocrinologist at UC San Diego Health, in California.
"Anecdotally, in my practice I don't see the profound weight loss and I haven't [seen] patients...coming completely off of their diabetes medication," she added. "We see that with the bariatric surgery population. I just haven't seen the profound weight loss with testosterone therapy."
Consider T Screening of Men With Diabetes and Hypogonadism Symptoms
The American College of Endocrinology and American Association of Clinical Endocrinologists began recommending that testosterone be measured in men with obesity and/or type 2 diabetes in their 2016 guidelines for the management of obesity, Saad noted.
And the American Diabetes Association 2018 Standards of Medical Care in Diabetes recommend that "for men with diabetes who have symptoms or signs of hypogonadism such as decreased sexual desire (libido) or activity or erectile dysfunction, consider screening with a morning serum testosterone" (B level of evidence).
The current study is based on data from a registry started in 2004 by two independent German urologists to assess the efficacy and safety of a new testosterone preparation, Saad explained.
The registry was not designed to study the effects of testosterone on type 2 diabetes, Saad stressed. "A remission of type 2 diabetes with testosterone has not been described in the literature. It was completely unexpected."
Saad and colleagues identified 133 men in the registry (a third of the patients) who had hypogonadism (testosterone ≤ 12.1 nmol/L) and type 2 diabetes.
All men received two injections of testosterone undecanoate at baseline and 6 weeks, followed by injections of 1000 mg testosterone every 3 months.
They were a mean age of 60 years and were all receiving metformin; five were also receiving insulin.
The 133 patients were followed for a mean 6.9 years (maximum 11 years).
The 16 patients (12%) who went into diabetes remission had been receiving testosterone for a mean 8.9 years.
One of the five patients on insulin had their insulin therapy stopped after 11 years of testosterone therapy.
And importantly, after an additional 6 months of follow-up, until mid-2018, 15 more patients attained diabetes remission, for a total of 31 patients (22%), Saad reported.
The Longer the Testosterone Therapy, the Better
"This indicates that the longer patients are treated with testosterone, the better the result and the higher the chance to go into remission," Saad said.
Among the initial 12% of patients who had diabetes remission, mean HbA1c dropped from 8.3% to 5.7%; fasting insulin declined from 24.7 to 7.6 μU/mL; HOMA-IR dropped from 8.7 to 1.8, and triglycerides decreased from 3.2 to 2.2 mmol/L.
Patients' weight also declined steadily from a mean of 107 to 89 kg, and waist circumference shrank from 108 to 97 cm, from baseline until end of follow-up.
Although bariatric surgery results in rapid, substantial weight loss, testosterone therapy is associated with a weight loss of 20% or more over a longer time, said Saad.
"Our patients have not missed a single injection, and this high motivation is due to the fact that patients feel a lot better," he said.
"They have more energy, their sexual function is improved, etc. That is why we do not have any dropouts in a study that started back in 2004."
No Cardiovascular Harm, Diverse Patients, More Remission
Santos Cavaiola asked Saad how they reconciled the benefits in weight loss and glycemic control with a possible concern for cardiovascular risk — although not proven — with testosterone therapy.
"After almost 14 years of study," Saad replied, cardiovascular outcomes and mortality was worse in a separate control group of hypogonadal patients who did not receive testosterone.
There were more than 60 myocardial infarctions and strokes in the untreated group, but "until today we didn't have a single stroke or myocardial infarction in the people on long-term testosterone treatment. So in our experience, everything that was said about cardiovascular risk increased by testosterone treatment is nonsense!" he observed.
Other members of the audience wanted to know more about the type of patients and their testosterone levels before and after treatment.
"This is a mixed group" with congenital hypogonadism, Klinefelter syndrome (30 to 40 patients), and young patients who had had an orchiectomy for testicular cancer, but "only 5% of these hypogonadal patients had a normal weight," Saad said.
Most patients had secondary hypogonadism as a consequence of obesity and chronic disease.
Their testosterone levels were initially about 10 nmol/L (300 ng/dL) and trough levels were about 600 to 700 ng/dL (18 nmol/L), "so we treat until the upper normal range."
And the fact that the latest data show over a fifth of the patients attained diabetes remission could be “a result of the fact that the diabetes center which is in charge of treating diabetes in our patients feels more and more at ease to take testosterone patients off their anti-diabetic medication," he speculated.
The study was supported by Bayer. Saad is an employee of Bayer and holds shares in Bayer, Novo Nordisk, and AbbVie. Santos Cavaiola has no relevant financial disclosures.