Obesity and metabolic impairments are widespread in both psychiatric and non-psychiatric populations. To make matters worse, weight gain, hyperlipidemia, and diabetes are common side effects of the pharmaceuticals we use to treat psychiatric illness. Exercise and diet can be effective interventions, but pharmacological options are scarce. Metformin, a common diabetes medication known to decrease hepatic gluconeogenesis and improve insulin sensitivity, has been studied for weight loss in nondiabetic patients.
To determine whether adjunctive metformin might cause weight loss in overweight patients with schizophrenia or schizoaffective disorder, researchers randomized 148 patients to metformin or placebo, in addition to their normal psychotropic regimen. All patients underwent weekly diet and exercise counseling. At baseline, patients were on at least one antipsychotic medication and all were overweight (BMI≥27). None had diabetes. At the end of 16 weeks, those who had taken metformin experienced, on average, a 3 kg (6.6 lb) weight loss, while those on placebo lost an average of 1 kg (2.2 lb). Metformin was also effective in reducing triglycerides (-7 mg/dL compared to +13 mg/dL for placebo) and HbA1c (-0.06% vs +0.01%), while other lipid parameters and glucose or insulin levels were not significantly different.
All patients received weekly diet and exercise counseling, which seemed effective, as the placebo group lost 0.3 BMI points over the course of the trial. Metformin caused an additional weight loss, which increased over time. Whether the weight loss caused by metformin might persist or increase after 16 weeks is unknown.
The results suggest that metformin, at daily doses up to 2,000 mg/d (1000 mg BID) over a 4-month period, can cause weight loss in patients with psychotic disorders. Metformin was well tolerated, with only nausea as a common, transient, side effect. Patients at risk for lactic acidosis, a known adverse effect of metformin, were excluded from the study.
While it is tempting to conclude that metformin may prevent or reverse the weight gain caused by antipsychotics, this was not the focus of this study. Indeed, all subjects were on antipsychotic medication for the duration of the trial, but there was no determination as to whether their baseline obesity had been caused by antipsychotics (Jarskog LF et al, Am J Psychiatry 2013;170(9):1032–1040).
TCPR’s TAKE: This study shows that metformin may cause a statistically significant weight loss and improvement in triglycerides in overweight patients with psychosis, and that diet and exercise counseling may also result in significant (although smaller) weight loss. It does not demonstrate that metformin can reverse the weight gain caused by antipsychotics, nor that it can be used prophylactically to prevent antipsychotic-associated weight gain.