In men who are overweight or obese, adding testosterone therapy reduced glucose intolerance/T2DM
A industry-funded trial found improved glucose control in men randomized to testosterone injections, but some of its claims were exaggerated, and routine use of testosterone therapy to prevent or reverse type 2 diabetes is not recommended, an ACP Journal Club commentary said.
An industry-funded Australian trial randomized about 1,000 men who were diagnosed with either impaired glucose tolerance or diabetes based on oral glucose tolerance testing (OGTT) to either intramuscular injections of testosterone undecanoate or placebo (at baseline, at six weeks, and then every three months for two years). All study participants had a serum testosterone concentration of 14.0 nmol/L or lower but no pathological hypogonadism at baseline. Both groups received a lifestyle intervention. The study's results showed a significantly greater mean improvement in two-hour glucose levels in the testosterone group.
The study was published by The Lancet Diabetes & Endocrinology in January. The following commentary by Tomás P. Griffin, MB, BCh, BAO, MSc, and Sean F. Dinneen, MD, was published in the ACP Journal Club section of Annals of Internal Medicine on May 4.
In the T4DM trial, men treated with testosterone undecanoate plus a lifestyle program had reduced glucose intolerance at 2 years vs. men who only attended the lifestyle program. The primary outcomes of incidence of type 2 diabetes mellitus (T2DM) and change in 2-hour glucose on OGTT were based on single 2-hour glucose values. OGTTs are prone to errors, and OGTT levels compared across multiple centers are not reliable. In the absence of diabetes symptoms or unequivocal hyperglycemia, the American Diabetes Association advocates 2 abnormal test results to diagnose diabetes. In a trial, it would be prudent to use a combination of parameters to diagnose diabetes in otherwise asymptomatic men. A treatment effect was seen for 2-hour fasting glucose but not for hemoglobin A1c, which better represents glycemic status over a 3-month period.
The authors' claims of reversing T2DM are exaggerated, as is the account of the study on the pharmaceutical sponsor's website. In men who had T2DM at baseline, the relative risk for a 2-hour OGTT glucose level ≥11.1mmol/L (≥199.8 mg/dL) did not differ between groups. The proportion of patients with well-controlled diabetes due to treatment with antihyperglycemic agents was not reported.
On the basis of available evidence and a lack of long-term safety data, routine use of testosterone therapy to prevent or reverse T2DM is not recommended. In 2008, the U.S. Food and Drug Administration mandated the completion of cardiovascular (CV) outcome trials/meta-analyses to evaluate the CV safety of drugs used to treat T2DM. The T4DM trial excluded patients at high risk for CV disease, reducing the generalizability of the results and the possibility of detecting an adverse CV signal due to the anticipated low incidence of CV events. Hematocrit was found to be elevated in 22% of the testosterone group compared with 1% of the placebo group—increased hematocrit itself is a risk factor for CV disease. Prolonged follow-up and CV outcome trials are needed before advocating routine use of testosterone in men without overt hypogonadism.