Testosterone, Lifestyle Program Reduce Risk of Type 2 Diabetes in Men
JUNE 17, 2020
Gary Wittert, MBBch, MD
The findings were presented as part of the American Diabetes Association’s (ADA’s) 80th Virtual Scientific Sessions.
Gary Wittert, MBBch, MD, and a team of investigators hypothesized testosterone treatment for 2 years would prevent progression to, or reverse, type 2 diabetes in high-risk men who were also enrolled in a community-based lifestyle program. They also predicted testosterone treatment for 2 years would lead to metabolically favorable changes in body composition, improve sexual function, and enhance adherence to the lifestyle program.
The investigators conducted a randomized, placebo-controlled, double-blind, two-year, phase 3b trial at 6 Australian tertiary care centers. Wittert and the team included adults aged 50-74 years old with a waist circumference >95 cm, oral glucose tolerance test two-hour score between 7.8-15 mmol/L (140-270 ng/dL), and serum testosterone concentration <14 mmol/L (404 ng/dL).
The lifestyle program was delivered by WW, formerly called Weight Watchers. Participants could attend group meetings, log onto the interactive website, or do both.
“The reason for Weight Watchers is because it has been shown to have benefit and efficacy and cost-efficacy for reducing the incidence of type 2 diabetes in men and is, in fact, more cost-effective than general practice and widely accessible to our participants,” Wittert said during a presentation of his team’s data.
The study treatment was testosterone undecanoate 1000 mg IMI given to participants at each study visit—baseline, 6 weeks, and 3 monthly for the rest of the 2 years.
Wittert and team randomized patients 1:1. Patients were stratified by center, age group (50-59 or 60-74 years old), waist circumference (95-100, 101-115, or >115 cm), two-hour glucose on the oral glucose tolerance test (7.8-9.5, 9.6-11, or 11.1-15 mmol/L), smoking (yes or no), and first-degree family history of type 2 diabetes (yes or no).
There were 2 primary endpoints, 1 of which was the proportion of patients with oral glucose tolerance test value for two-hour glucose >11.1 mmol/L from 16% in the control group to 9% in the testosterone group (significance level, 3.5%). The other endpoint was mean change from baseline in two-hour glucose of .6 mmol/L (10.8 mg/dL) based on SD 2.42 mmol/L (43.56 mg/dL) (significance level, 2.5%).
Overall, 19,000 men were screened and 1007 were randomized (placebo=503 men; testosterone=504 men). There were slightly more discontinuations among the placebo group than the testosterone group (26% vs 23%). In both groups, 20% of patients were newly diagnosed with type 2 diabetes at baseline.
In measuring the first primary outcome of proportion with two-hour glucose >11.1 mmol/L, 21.1% in the placebo group and 12.4% in the testosterone group (RR, .59; 95% CI, .43-.8; P <.001). Adjusted analyses for baseline included a RR of .61 in the testosterone group (95% CI, .45-.84; P=.002). After adjusting for risk factors, the RR was .65 (95% CI, .5-.86; P=.002).
For the second primary outcome, mean change in two-hour glucose at 2 years, there was a -.95 mmol/L change in the placebo group and a -1.7 mmol/L change in the testosterone group (mean difference, -.75; 95% CI, -1.1 to -.4; P <.001). After adjusting for baseline, the testosterone RR was .69 (95% CI, -1.05 to -.33; P <.001). When adjusted for risk factors, the RR was -.71 (95% CI, -1.07 to -.35; P <.001).
Testosterone decreased the risk of type 2 diabetes at 2 years by approximately 40% beyond the lifestyle program alone. There were also favorable changes in body composition, small benefits for sexual function, and reassurance for cardiovascular safety.
“Men will be best served with a comprehensive and personalized approach to healthcare that includes a thorough assessment of physical and psychological conditions and risk factors, and optimization of health-related behaviors,” Wittert concluded.
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 published as part of ADA 2020.