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Objective:   To assess whether metformin prevents body weight gain (BWG) and metabolic dysfunction in patients with schizophrenia who are treated with olanzapine.Method:   Forty patients taking olanzapine (10 mg daily) were randomly allocated to a metformin ( n = 20; 850 to 1700 mg daily) or placebo ( n = 20) group in a 14-week double-blind study. Waist circumference (WC), BWG, body mass index (BMI) fasting glucose, insulin, and lipids were evaluated at baseline and at Weeks 7 and 14 of treatment.Results:   At Week 14, BWG (kg) was similar in the metformin group (5.5 kg) and the placebo group (6.3 kg), P = 0.4. There were no differences between the changes in BMI, WC, glucose, insulin, insulin resistance index (HOMA-IR), and plasma lipid levels observed in the treatment group and the placebo group; however, glucose levels decreased significantly after metformin administration ( P = 0.02). The HOMA-IR decreased significantly in both groups, but 3 subjects from the placebo group developed fasting glucose levels greater than 5 mmol/L. After taking metformin, triglyceride levels increased, but the cholesterol profile improved significantly.Conclusions:   Metformin did not prevent olanzapine-induced BWG. While some lipid parameters worsened during placebo, the HOMA-IR improved in both the placebo and the metformin groups. Carbohydrate metabolism impairment was not systematically observed during short-term olanzapine administration.

Metformin for Prevention of Weight Gain and Insulin Resistance with Olanzapine: A Double-Blind Placebo-Controlled Trial