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Weight Gain with Olanzapine: Does Metformin Help?

Patients lost a little, but not enough to make a difference.

Patients gain a lot of weight with atypical antipsychotics; one recent study found an average gain of more than 37 pounds with olanzapine (Journal Watch Psychiatry Aug 27 2007). Few placebo-controlled studies have been conducted into possibly helpful medications. Because some patients taking atypicals develop the metabolic syndrome, which includes problems of glycemic control, metformin has been proposed as a potential treatment; however, results have been inconsistent (for a pediatric study, see Journal Watch Psychiatry Jan 12 2007). Recently, investigators in Venezuela performed a 12-week, randomized, placebo-controlled trial in 80 patients (60 inpatients, 76 diagnosed with schizophrenia) who had been receiving treatment with olanzapine for more than 4 months. Add-on metformin was started at 850 mg and was increased to a maximum of 2550 mg/day.

Most patients spontaneously increased their physical activity and improved their diet. Weight loss was significant from baseline to 12 weeks within the metformin group (mean, 1.40 kg), but in the comparison with the placebo group, the difference was only marginally significant (P=0.09; mean loss with placebo, 0.18 kg). Glucose and insulin levels were unchanged. A measure of insulin resistance did not change in the metformin group but increased in the placebo group. Leptin levels tended to decrease with metformin.

Comment: A slight increase in weight loss was associated with the use of metformin in this study. However, a loss of 3 pounds does not seem like a noteworthy improvement if the weight gained was more than 30 pounds. These results make it difficult to justify initiation of metformin after weight gain in patients taking olanzapine.

— Jonathan Silver, MD

Published in Journal Watch Psychiatry August 27, 2007

Citation(s):

Baptista T et al. Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: A multicentric, double-blind, placebo-controlled trial. Schizophr Res 2007 Jul; 93:99-108.

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