A Naturalistic Randomized Placebo-Controlled Trial of Extended-Release Metformin to Prevent Weight Gain Associated With Olanzapine in a US Community-Dwelling Population.

ABSTRACT

OBJECTIVE: This 24-week pilot study assessed the efficacy, tolerability, and safety of adjunctive metformin versus placebo for the prevention of olanzapine-associated weight gain in community-dwelling adult patients with schizophrenia, schizoaffective disorder, bipolar disorder, or major depression with psychotic features. METHODS: In a double-blind study, 25 patients were randomly assigned to receive 24 weeks of either olanzapine plus metformin or olanzapine plus placebo. Metformin extended release was titrated to 2000 mg daily as tolerated. No other antipsychotics were allowed, whereas psychotropic medications including antidepressants and mood stabilizers were permitted. The primary outcome measures were change in body weight and homeostatic model assessment for insulin resistance from baseline to week 24. RESULTS: The intent-to-treat population comprised patients who had 1 or more post-baseline visit. Mean change in body weight for the olanzapine plus metformin (O/M) group was 5.5 lb, which was less than the 12.8 lb gain for the olanzapine plus placebo (O/P) group (P < 0.05). Compared with O/P group who gained 7% of their body weight, patients in the O/M group gained 3% (P < 0.037). Body mass index change in the O/M group was 0.85 versus 2.02 in the O/P group (P < 0.045). There was a trend for a greater increase in baseline to end point homeostatic model assessment for insulin resistance and waist circumference in the O/P group versus the O/M group. CONCLUSIONS: In this naturalistic sample of typical US community-dwelling patients, metformin was effective and well tolerated for the prevention of olanzapine-associated weight gain. Adjunctive metformin should be studied in a similar but larger population to determine its role in the prevention of olanzapine-associated weight gain.