Diabetes Drug Reverses SGA-Related Weight Gain

Taking metformin with antipsychotic drugs, may counteract the weight gain and possible diagnosis of diabetes. A new study has come to the same conclusion as two earlier reports: a common diabetes medication, metformin (Glucophage), appears to be effective at blocking the sometimes significant weight gain associated with second-generation antipsychotic medications (SGAs). What was new in the latest report was the age of the patients in the study: children and adolescents aged 10 to 17.

The report by David klein, M.D., Ph.D., an associate professor of medicine and pediatric endocrinology at the Cincinnati Children’s Hospital Medical Center, and colleagues conducted a protocol known as an "add-on, parallel-design trial" in which they enrolled 39 patients aged 10 to 17 who had been taking one of three SGAs—olanzapine, quetiapine (Seroquel), or risperidone (Risperdal)—for up to one year and had gained more than 10 percent of their pretreatment body weight while on the SGA.

At the beginning of the study, each of the 39 patients was randomly assigned to having either metformin or a matched placebo added to their SGA regimen for 16 weeks. At baseline, and at weeks 4, 8, 12, and 16, several measures were examined including height, weight, waist circumference, a series of laboratory tests, and screening for adverse events.

At study completion those who were randomly assigned to placebo had gained an average of 8.8 pounds and had an average increase in body mass index (BMI) of 2.4 pounds/m2 (see graph top right). Those who took metformin along with their SGA, on average, lost 0.26 pounds and had an average decline of 0.9 pounds/m2 in their BMI. In addition, measures of insulin resistance—a potential precursor to diabetes—increased significantly in those on placebo while remaining stable in those taking metformin

"The results are notable," Towbin said, "for the clear differences between treatment groups in average weight gain, absolute BMI… [and] there were impressive changes in measures of insulin resistance."

While Towbin called the report "a welcome investigation addressing a serious problem," and stated that the "findings are good news," he qualified his comments by noting that "any zeal should be tempered." The study does not address the long-term safety of metformin, for example, or whether the weight loss is sustained.

Yet Doraiswamy, who is an expert on the association between SGAs and metabolic adverse effects, added, "Before we debate whether or not to add metformin to minimize metabolic side effects, our first priority should be large clinical trials to prove the [SGAs] are effective in children. Otherwise, we will be putting the cart before the horse."

"A Randomized, Double-Blind, Placebo-Controlled Trial of Metformin Treatment of Weight Gain Associated With Initiation of Atypical Antipsychotic Therapy in Children and Adolescents" https://ajp.psychiatryonline.org/cgi/content/abstract/163/12/2072 Psychiatr News January 5, 2007, Volume 42, Number 1, page 17