The Effect of Metformin on Anthropometrics and Insulin Resistance in Patients Receiving Atypical Antipsychotic Agents: A Meta-Analysis

University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 04/2010; 71(10):1286-92. DOI: 10.4088/JCP.09m05274yel
Source: PubMed

ABSTRACT In the Clinical Antipsychotic Trials of Intervention Effectiveness, atypical antipsychotics (AAPs) were found to be associated with weight gain and impairment of glucose metabolism. While metformin has been shown to attenuate weight gain and insulin resistance, not all studies have shown a benefit in the reduction of antipsychotic-induced weight gain and insulin resistance.
To characterize metformin's impact on anthropometrics and insulin resistance in patients taking AAPs.
A systematic literature search of MEDLINE, EMBASE, and Cochrane CENTRAL was conducted from the earliest possible date through December 31, 2008. The search was performed using the following Medical Subject Headings and text keywords: metformin, biguanide(s), in combination with neuroleptic(s), neuroleptic drug(s), antipsychotic(s), dopamine antagonist(s), atypical antipsychotic(s), psychotropic(s), risperidone, olanzapine, quetiapine, ziprasidone, sulpiride, clozapine, iloperidone, aripiprazole, paliperidone, melperone, bifeprunox, amisulpride, zotepine, and sertindole.
Six of 62 identified studies (N = 336 participants) met our inclusion criteria: randomized, placebo-controlled trials of metformin in patients taking AAPs with data on weight, body mass index (BMI), waist circumference, insulin resistance (determined using the homeostasis model assessment of insulin resistance [HOMA-IR]), and/or a diagnosis of diabetes.
Data were independently abstracted by 2 investigators; disagreements were resolved through discussion or by a third investigator using a standardized data abstraction tool. For continuous endpoints, the weighted mean difference (WMD) of the change from baseline with 95% CI was calculated as the difference between the mean in the metformin and placebo groups. For categorical endpoints, the pooled relative risk (RR) with 95% CI was calculated. A random-effects model was used for all analyses.
Compared to placebo, the metformin group had significantly reduced weight (WMD, 3.16 kg; P = .0002), BMI (WMD, 1.21 kg/m²; P = .0001), waist circumference (WMD, 1.99 cm; P = .005), and HOMA-IR (WMD, 1.71; P = .004). The reduction in risk of diabetes was not statistically significant (RR, 0.30; P = .13).
This analysis suggests that using metformin in patients treated with AAPs may reduce metabolic risks. Additional randomized controlled trials are needed, but available data support consideration of this intervention in clinical practice.

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    • "Previous studies have indicated that activating AMPK with metformin (a classic approach to treat the metabolic syndrome) confers a disappointingly small beneficial effect against some of the metabolic effects of OLZ (Ehret et al., 2010 "
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    • "For example, in 2007, Wu and colleagues[6] reported that metformin can effectively mitigate antipsychotics-induced weight gain and abnormal glucose metabolism and several other studies in China report similar findings.[7]–[11] A meta-analysis reported in 2010[12] found that metformin can reduce weight, body mass index (BMI), waist circumference and insulin resistance, but did not reduce the incidence of diabetes in patients using antipsychotics. "
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    • "Current therapy for OL-associated BWG along with the glucose and lipid dysregulation has focused on dietary caloric restriction (which has limited efficacy even in patients without the psychopathology of schizophrenia), weight loss medications (many of which are contraindicated because of CNS side effects) e.g. sibutramine (Henderson et al., 2005) and the frequent use of metformin (Ehret et al., 2010; Praharaj et al., 2011) that may be superior to the other agents particularly when impaired glucose tolerance or type 2 diabetes develops (Bushe et al., 2009). Also, reboxetine (Poyurovsky et al., 2003) and topiramate (Narula et al., 2010) additions to ongoing OL treatment resulted in significant attenuation of BWG, whereas fluoxetine (Poyurovsky et al., 2002) or famotidine (Poyurovsky et al., 2004) proved to be ineffective. "
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