Metformin for prevention of weight gain and insulin resistance with olanzapine: A double-blind placebo-controlled trial

Department of Physiology, Los Andes University Medical School, Mérida, Venezuela.
Canadian journal of psychiatry. Revue canadienne de psychiatrie (Impact Factor: 2.55). 04/2006; 51(3):192-6.
Source: PubMed


To assess whether metformin prevents body weight gain (BWG) and metabolic dysfunction in patients with schizophrenia who are treated with olanzapine.
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.
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.
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.

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    • "Furthermore, the average weight gains after 10-week treatments with clozapine and olanzapine were 3.99 and 3.51 kg, respectively (Allison et al. 1999). The mechanisms responsible for these side effects are poorly understood and are not prevented by any of the agents that are routinely used to treat type 2 diabetes (Baptista et al. 2006; Dwyer and Donohoe 2003). In addition to promoting weight gain, metabolic syndrome, and diabetes, the side effects of atypical antipsychotics result in poor compliance and interfere with effective treatment of psychiatric disease. "
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    ABSTRACT: Weight gain and dysfunction of glucose and lipid metabolism are well-known side effects of atypical antipsychotic drugs (AAPD). Here, we address the question whether a heat-shock protein (HSP) co-inducer, insulin sensitizer drug candidate, BGP-15, can prevent AAPD-induced glucose, lipid, and weight changes. We also examined how an AAPD alters HSP expression and whether BGP-15 alters that expression. Four different experiments are reported on the AAPD BGP-15 interventions in a human trial of healthy men, a rodent animal model, and an in vitro adipocyte cell culture system. Olanzapine caused rapid insulin resistance in healthy volunteers and was associated with decreased level of HSP72 in peripheral mononuclear blood cells. Both changes were restored by the administration of BGP-15. In Wistar rats, weight gain and insulin resistance induced by clozapine were abolished by BGP-15. In 3T3L1 adipocytes, clozapine increased intracellular fat accumulation, and BGP-15 inhibited this process. Taken together, our results indicate that BGP-15 inhibits multiple metabolic side effects of atypical antipsychotics, and this effect is likely to be related to its HSP co-inducing ability.
    Cell Stress and Chaperones 02/2012; 17(4):517-21. DOI:10.1007/s12192-012-0327-5 · 3.16 Impact Factor
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    • "Klein and colleagues, in their randomized, double-blind, placebo-controlled trial of metformin in children and adolescents taking atypical antipsychotics , found arrested weight gain, as well as improved insulin resistance (Klein et al. 2006). Whereas Baptista and associates found that metformin did not prevent olanzapineinduced weight gain in a group of adult patients with schizophrenia (Baptista et al. 2006), Wu and colleagues published two studies indicating that metformin, administered to a group of adult patients with schizophrenia on antipsychotics , including olanzapine, was effective in attenuating "
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    ABSTRACT: Metformin was assessed as an interventional medication for weight gain in children and adolescents taking atypical antipsychotic agents. A 12-week open-label trial was conducted to evaluate metformin's effectiveness and safety for weight management. Eleven subjects, ages 10-18 years, participated in the study. Each subject received metformin orally up to 2000 mg/day. Primary outcome measures included weight, body mass index (BMI), and waist circumference. Secondary outcome measures included serum glucose, insulin, and fasting lipid profile. Changes in weight, BMI, waist, and metabolic profile were obtained by using repeated measures of covariance. The mean reduction in weight, waist, BMI, serum glucose, and serum insulin was not statistically significant. However, 5 out of 11 patients lost weight (mean, -2.82 kg +/- 7.25), and overall the sample did not continue to gain weight. There was a significant decrease in triglyceride levels. Metformin was fairly well tolerated. Preliminary data suggests that metformin may safely and effectively improve the triglyceride profile. However, contrary to study hypotheses, weight, waist, and BMI reduction were not statistically significant. Future double-blind studies with larger sample sizes and of longer duration are warranted to assess more fully the safety and efficacy of this intervention.
    Journal of child and adolescent psychopharmacology 07/2009; 19(3):275-9. DOI:10.1089/cap.2008.094 · 2.93 Impact Factor
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    • "In the second, an open-label study, metformin significantly decreased body weight in 19 pediatric patients taking psychotropic drugs (Morrison et al., 2002). In the third, a double-blind, placebocontrolled study, metformin did not prevent the olanzapineinduced weight gain after 14-week trial (Baptista et al., 2006, 2007b). In the fourth, a 16-week double-blind placebo-controlled trial revealed that metformin is safe and effective in treating the weight gain and insulin resistance associated with the antipsychotic use in children and adolescents (Klein et al., 2006). "
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    ABSTRACT: The second generation antipsychotic drugs, such as risperidone, olanzapine, and quetiapine, are effective in treating patients with schizophrenia and have been considered as the first line therapy. Recently, increasing attention has been drawn to the potential diabetogenic effect of these novel antipsychotics. The goal of this study was to evaluate the effect of metformin treatment on the olanzapine-induced metabolic disturbance in schizophrenic patients. Twenty-four schizophrenic subjects who had received olanzapine treatment at least 3 months were assigned to the therapy with metformin 1500 mg/day for 8 weeks. The metabolic parameters were quantitatively assessed at baseline, weeks 2, 4, and 8 by using the intravenous glucose tolerance test. After an 8-week treatment with metformin, the body weight, fasting levels of glucose, triglyceride, and insulin, insulin secretion, and insulin resistance significantly decreased. Half of study subjects with metabolic syndrome obtained improvement after the metformin trial. Subjects' psychopathological condition remained unchanged during the study period. The olanzapine-induced metabolic disturbance could be reversed after 8-week metformin treatment. Based on the results of this study, we hypothesize that metformin could modulate the effect of olanzapine-induced metabolic disturbance.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2008; 32(4):925-31. DOI:10.1016/j.pnpbp.2007.11.013 · 3.69 Impact Factor
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