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Metformin for weight gain associated with second generation antipsychotics in children and adolescents: a systematic review and meta-analysis

Metformin for weight gain associated with second generation antipsychotics in children and adolescents: a systematic review and meta-analysis
Metformin for weight gain associated with second generation antipsychotics in children and adolescents: a systematic review and meta-analysis
Background:Weight gain is a potentially concerning side effect of second-generation antipsychotics (SGAs). Metformin, a biguanide with antihyperglycemic effects, is used to manage weight gain in adults treated with SGAs.Objective:The objective of this study was to perform the first systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of metformin on weight gain in children and adolescents treated with SGAs.Methods:Based on a pre-registered protocol (PROSPERO–CRD42017074839), we searched the PubMed, EMBASE, PsychoINFO, BIOSIS, Science Direct, Cochrane Central, and ClinicalTrials.gov electronic databases through March 2018 (with no restrictions on language, date, or type of publication) for RCTs that assessed the effect of metformin or placebo on body weight in children or adolescents (< 18 years of age) treated with selected SGAs (risperidone, aripiprazole, olanzapine, and clozapine) for any psychiatric disorder. We also contacted relevant drug manufacturers for possible additional pertinent studies/data. A random effects model was used and the quality of the included RCTs was assessed using the Cochrane Risk of Bias tool.Results:Five RCTs (205 participants in total) were included in the meta-analysis. We found a significant weight decrease in the metformin group compared with placebo after 4, 12, and 16 weeks of treatment {mean difference − 0.98 kg (95% confidence interval [CI] − 1.26, − 0.69); − 1.83 kg (95% CI − 2.47, − 1.18); and − 3.23 kg (95% CI − 5.59, − 0.86), respectively}. A weight decrease at weeks 2 and 8 did not reach statistical significance. The decrease in body mass index (BMI) paralleled that of weight, with a significant effect at weeks 4, 12, and 16. Overall, four studies were rated as unclear, and one study was rated as high, risk of bias.Conclusion:Meta-analytical evidence shows that metformin might decrease weight in children/adolescents treated with SGAs but additional high-quality evidence is needed. Clinicians need to be aware that this use of metformin is currently off-label.
1172-7047
Ellul, Pierre
61d2a501-2d59-4895-935a-ad220e0e5433
Delorme, Richard
455473a3-f39d-44c3-957a-e98d017a8e60
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb
Ellul, Pierre
61d2a501-2d59-4895-935a-ad220e0e5433
Delorme, Richard
455473a3-f39d-44c3-957a-e98d017a8e60
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb

Ellul, Pierre, Delorme, Richard and Cortese, Samuele (2018) Metformin for weight gain associated with second generation antipsychotics in children and adolescents: a systematic review and meta-analysis. CNS drugs. (doi:10.1007/s40263-018-0571-z).

Record type: Article

Abstract

Background:Weight gain is a potentially concerning side effect of second-generation antipsychotics (SGAs). Metformin, a biguanide with antihyperglycemic effects, is used to manage weight gain in adults treated with SGAs.Objective:The objective of this study was to perform the first systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of metformin on weight gain in children and adolescents treated with SGAs.Methods:Based on a pre-registered protocol (PROSPERO–CRD42017074839), we searched the PubMed, EMBASE, PsychoINFO, BIOSIS, Science Direct, Cochrane Central, and ClinicalTrials.gov electronic databases through March 2018 (with no restrictions on language, date, or type of publication) for RCTs that assessed the effect of metformin or placebo on body weight in children or adolescents (< 18 years of age) treated with selected SGAs (risperidone, aripiprazole, olanzapine, and clozapine) for any psychiatric disorder. We also contacted relevant drug manufacturers for possible additional pertinent studies/data. A random effects model was used and the quality of the included RCTs was assessed using the Cochrane Risk of Bias tool.Results:Five RCTs (205 participants in total) were included in the meta-analysis. We found a significant weight decrease in the metformin group compared with placebo after 4, 12, and 16 weeks of treatment {mean difference − 0.98 kg (95% confidence interval [CI] − 1.26, − 0.69); − 1.83 kg (95% CI − 2.47, − 1.18); and − 3.23 kg (95% CI − 5.59, − 0.86), respectively}. A weight decrease at weeks 2 and 8 did not reach statistical significance. The decrease in body mass index (BMI) paralleled that of weight, with a significant effect at weeks 4, 12, and 16. Overall, four studies were rated as unclear, and one study was rated as high, risk of bias.Conclusion:Meta-analytical evidence shows that metformin might decrease weight in children/adolescents treated with SGAs but additional high-quality evidence is needed. Clinicians need to be aware that this use of metformin is currently off-label.

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Metformin_Manuscript_Reviewer_080818_SC - Accepted Manuscript
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Accepted/In Press date: 29 August 2018
e-pub ahead of print date: 20 September 2018

Identifiers

Local EPrints ID: 424459
URI: https://eprints.soton.ac.uk/id/eprint/424459
ISSN: 1172-7047
PURE UUID: 92bb3476-ed98-4ebc-a1c0-cb83289ced8c
ORCID for Samuele Cortese: ORCID iD orcid.org/0000-0001-5877-8075

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Date deposited: 05 Oct 2018 11:37
Last modified: 10 Dec 2019 05:13

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