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Obesity and cardiovascular disease risks are elevated in patients with schizophrenia and contribute significantly to premature death in these patients. Previous studies of metformin in schizophrenia patients have involved highly selected populations and have yielded inconsistent results. In this first-ever, randomized, controlled trial of metformin added to ongoing psychiatric medication, 148 typical outpatients with schizophrenia or schizoaffective disorder (mean age, 43) were randomized to 16 weeks of metformin (increased as tolerated to 1000 mg twice daily) or placebo.
All patients were taking one or two antipsychotics and received diet and exercise counseling. Patients with diabetes mellitus were excluded. At entry, participants had a mean weight of 101.9 kg (mean body-mass index, 34.6) and averaged marginally high triglyceride levels (150.3 mg/dL). Mean total, low-density and high-density lipoprotein cholesterol, and hemoglobin A1C levels were within normal ranges.
Completers included 77% of metformin patients and 82% of placebo patients. Metformin was associated with greater weight loss (3.0 vs. 1.0 kg with placebo; reduction in weight, 2.8% vs. 1.0%) and improvement in triglyceride levels (–7.0 vs. +13.2 mg/dL). Adherence to metformin was excellent, with no major related adverse events.
Jarskog LF et al. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder. Am J Psychiatry 2013 Jul 12; [e-pub ahead of print]. (http://dx.doi.org/10.1176/appi.ajp.2013.12010127)
Comment
This study did not standardize diet or extent of exercise. Still, in this population, add-on metformin was associated with modestly improved weight and triglyceride levels. The differences in triglyceride levels seem particularly noteworthy. Other research suggests that patients taking metformin for longer periods are likely to experience even greater weight loss and metabolic improvement. In this study, the differences in triglyceride levels seem particularly noteworthy. How much these modest changes might improve health outcomes in the long run remains to be seen, but with few other options and metformin's few adverse effects, psychiatric practitioners should become comfortable in prescribing this medication.