Metformin May Help Combat Antipsychotic-Induced Weight Gain

In a new meta-analysis, researchers have found the drug metformin appears to be the most effective pharmacological option for countering weight gain related to the use of antipsychotic medications.

Metformin is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes.

The senior researcher was Hiroyuki Uchida of Keio University School of Medicine in Tokyo, and study results were published online March 17 in Schizophrenia Bulletin.

Since antipsychotic-induced weight gain is often difficult to manage, and using concomitant medications to counteract such weight gain might be a rational option, Uchida and his colleagues analyzed scientific literature on the topic to determine which medications might be able to reverse such weight gain.

The researchers pooled the effects of 40 studies that had been published up to November 2013 and that evaluated 19 interventions for antipsychotic-induced weight gain. The primary outcome was a change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose levels, hemoglobin A1c, fasting insulin levels, insulin resistance, and levels of cholesterol and triglycerides.

Metformin was the most extensively studied drug in regard to countering antipsychotic-induced weight gain, they found. It also appeared to be the most effective of the medications studied, resulting in an average body weight loss of 3.17 kg compared with patients taking a placebo.

Subjects receiving aripiprazole, reboxetine, or topiramate to counter antipsychotic-induced weight gain also weighed significantly less than those getting a placebo. For example, three studies reported on the effects of add-on aripiprazole as a weight-controlling agent. The average weight difference amounted to a reduction of 2.13 kg compared with placebo.

In addition, both metformin and rosiglitazone, another antidiabetes drug, improved insulin resistance, while aripiprazole and metformin decreased blood lipids.

“When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia,” Uchida and colleagues concluded.

Commenting on the study, William Carpenter, M.D., director of the Maryland Psychiatric Research Center at the University of Maryland and a schizophrenia expert, told Psychiatric News , “Schizophrenia is like a perfect storm for metabolic syndrome, and reduced life span is alarming. Metabolic abnormalities are associated with the illness, then lifestyle behavioral risks are added, and finally the adverse effects of many antipsychotic drugs. Uchida and colleagues provide clinicians with a comprehensive review on the role of medications to address metabolic abnormalities associated with schizophrenia.”

“Obesity and associated metabolic consequences represent a serious concern in patients with schizophrenia,” Deanna Kelly, Pharm.D., director and chief of the Treatment Research Program at the Maryland Psychiatric Research Center, pointed out. “Attenuation and reversal of weight gain is difficult, and behavioral modifications are challenging in this population. Accumulating evidence, as in this meta-analysis, suggests that some pharmacologic treatments may help attenuate weight gain. Metformin, despite its modest ability to attenuate weight gain, may be an important addition for many patients who are at risk for weight and related consequences.”

No outside funding was used for this study. ■

An abstract of “Pharmacological Strategies to Counteract Antipsychotic-induced Weight Gain and Metabolic Adverse Effects in Schizophrenia: A Systematic Review and Meta-analysis” can be accessed here.