Testosterone therapy reduces diabetes risk in obese and overweight men
Delhi: Overweight and obese men administered with a combination of testosterone therapy and participation in a lifestyle program had a lower risk of developing type 2 diabetes, improved sexual function, and satisfaction, according to a recent study. The findings of the study were presented at the virtual 80th Annual Scientific Sessions of the American Diabetes Association.
Gary A. Wittert, the University of Adelaide, Australia, and colleagues tested the hypotheses whether 1) testosterone treatment for two years will prevent progression to, or reverse, type 2 diabetes in high-risk men concurrently enrolled in a community-based lifestyle program 2) that testosterone treatment for two years will lead to metabolically favorable changes in body composition, improve sexual function, and enhance adherence to the lifestyle program.
The study was based on the observation that low serum testosterone is an independent risk factor for type 2 diabetes in obese and overweight men.
The study included men aged 50 to 74 years with a waist circumference > 95 cm, a baseline serum testosterone concentration ≤ 14 nmol/L, and a 2-hour oral glucose tolerance test (OGTT) of 7.8 to 15.0 mmol/L. They were randomized in the ration 1:1 to receive an intramuscular injection of testosterone undecanoate 1000 mg or placebo. All patients also participated in a program delivered by WW (formerly Weight Watchers) -- consisting of weekly in-person group meetings, interactive website participation, or both.
Testosterone/placebo was administered at baseline, at 6 weeks, and then three times per month, coinciding with study visits, for 2 years. Patients were followed for a total of 2 years and were stratified by study center, age group, waist circumference, 2-hour OGTT, smoking habits, and family history of type 2 diabetes.
The co-primary endpoints were the proportion of participants with 2-hour OGTT ≥ 11.1 mmol/L and a difference in mean 2-hour OGTT ≥ 0.6 mmol/L between treatments at 2 years. Secondary endpoints were change in body composition and sexual function from baseline as well as normalization of blood glucose (2-hour glucose < 7.8 mmol/L).
Of 19,022 screened patients, 1007 were enrolled in the trial. A total of 82.1% of placebo patients and 87.9% of testosterone patients completed the 2-year follow-up period. Major reasons for patient withdrawal in both arms were raised hematocrit and voluntary withdrawal initiated by the patient.
Key findings of the study include:
- Compliance in the lifestyle program was low but similar for both groups (30% in the testosterone group and 28% in the placebo group).
- Two-hour OGTT ≥ 11.1 mmol/L was observed among 12.4% of patients who received testosterone and 21.1% of those on placebo, for a relative risk ratio of 0.59. Results were similar even after controlling for baseline testosterone level and risk factors for diabetes.
- Mean change in 2-hour OGTT was -1.70 mmol/L for testosterone patients and -0.95 mmol/L for placebo patients, for a mean difference of -0.75.
- A mean difference of -0.69 was observed following adjustment for baseline testosterone, and -0.71 after adjusting for baseline risk factors.
- Reduction from baseline in average waist circumference was 2.1 cm greater among those who received testosterone, compared with placebo.
- Patients treated with testosterone also had a greater decrease in total fat mass (2.7 kg) and abdominal fat percentage (2.3%) as well as greater increases in average total muscle mass of (1.7 kg), arm muscle mass of (0.36 kg), and handgrip strength (2.2 kg) than placebo.
- Testosterone-treated patients experienced an improvement in sexual function and satisfaction score, compared with placebo, including greater positive changes in erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall sexual satisfaction.
- The trend was toward negative changes in sexual functioning for most measures in the placebo group but positive for all measures in the testosterone group.
- Normalized blood glucose levels occurred in 51.9% of testosterone patients and 43.3% of placebo patients, for a relative risk ratio of 1.20.
- An increase in hematocrit ≥ 54% was experienced by 21.6% of testosterone patients and 1.2% of those on placebo.
- 55 adverse events were experienced by testosterone patients, while 42 events occurred in placebo patients, with the most common adverse events being ischemic heart disease, arrythmias, benign prostatic hyperplasia, prostate cancer, and other cancers. There were 2 deaths in each group.
"Testosterone decreased the relative risk of type 2 diabetes at 2 years by 40% beyond the lifestyle program alone. It was a pharmacological effect not related to baseline serum testosterone concentration. Testosterone treatment was also associated with favorable changes in body composition and small benefits for sexual function. Cardiovascular]safety was reassuring. However, there were frequent treatment-induced elevations of hematocrit, and so it is important to consider baseline risk factors that might be responsible for increasing hematocrit before prescribing testosterone." concluded the authors.
The study, "Effect of Testosterone Treatment on Type 2 Diabetes Incidence in High-Risk Men Enrolled in a Lifestyle Program: A Two-Year Randomized Placebo-Controlled Trial," was presented at ADA 2020.
