Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight

A 24-week, randomized, double-blind, placebo-controlled study

Chun Hsin Chen, Ming Chyi Huang, Chung Feng Kao, Shih Ku Lin, Po Hsiu Kuo, Chih Chiang Chiu, Mong Liang Lu

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Objective: Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia. Whether or not the beneficial effects can be sustained after discontinuation of metformin needs to be evaluated. We conducted a 24-week randomized, double-blind, placebo-controlled study to evaluate the effect of metformin on metabolic features in clozapine-treated patients with schizophrenia and followed their body weight after stopping the intervention for at least 24 weeks. Method: The study was conducted between September 2008 and July 2011. We recruited patients with DSM-IV diagnosis of schizophrenia or schizoaffective disorder who had been taking clozapine for more than 3 months, were overweight or obese, or fulfilled at least 1 criteria of metabolic syndrome. Eligible patients were randomized to receive metformin 1,500 mg/d or placebo. We followed metabolic features at baseline and at weeks 2, 4, 8, 16, and 24 and rechecked body weight when the patients stopped the trial after at least 24 weeks. Results: A total of 55 subjects (28 in the metformin and 27 in the placebo group) were enrolled. There were no significant differences in all baseline characteristics between the 2 groups, except that patients in the metformin group had higher fasting plasma glucose levels (P = .03). After the 24-week intervention, body weight (P <.0001), body mass index (P <.0001), fasting plasma glucose (P <.0001), high-density lipoprotein cholesterol (P = .03), insulin level (P = .01), and homeostasis model assessment index (P = .02) had significant changes in the metformin group. At the end of the intervention, 8 patients (28.57%) lost more than 7% of their body weight in the metformin group. Mean body weight returned to baseline after patients stopped the intervention in the metformin group. Conclusions: Metformin can significantly reduce body weight and reverse metabolic abnormalities in clozapine-treated patients with schizophrenia and preexisting metabolic abnormalities. However, the beneficial effects of metformin on body weight disappeared after discontinuing this medication. Trial Registration: ClinicalTrials.gov identifier: NCT01300637.

Original languageEnglish
JournalJournal of Clinical Psychiatry
Volume74
Issue number5
DOIs
Publication statusPublished - 2013

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Clozapine
Metformin
Schizophrenia
Placebos
Body Weight
Fasting
Glucose
Diagnostic and Statistical Manual of Mental Disorders
Psychotic Disorders
HDL Cholesterol
Body Mass Index
Homeostasis
Insulin

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

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title = "Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: A 24-week, randomized, double-blind, placebo-controlled study",
abstract = "Objective: Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia. Whether or not the beneficial effects can be sustained after discontinuation of metformin needs to be evaluated. We conducted a 24-week randomized, double-blind, placebo-controlled study to evaluate the effect of metformin on metabolic features in clozapine-treated patients with schizophrenia and followed their body weight after stopping the intervention for at least 24 weeks. Method: The study was conducted between September 2008 and July 2011. We recruited patients with DSM-IV diagnosis of schizophrenia or schizoaffective disorder who had been taking clozapine for more than 3 months, were overweight or obese, or fulfilled at least 1 criteria of metabolic syndrome. Eligible patients were randomized to receive metformin 1,500 mg/d or placebo. We followed metabolic features at baseline and at weeks 2, 4, 8, 16, and 24 and rechecked body weight when the patients stopped the trial after at least 24 weeks. Results: A total of 55 subjects (28 in the metformin and 27 in the placebo group) were enrolled. There were no significant differences in all baseline characteristics between the 2 groups, except that patients in the metformin group had higher fasting plasma glucose levels (P = .03). After the 24-week intervention, body weight (P <.0001), body mass index (P <.0001), fasting plasma glucose (P <.0001), high-density lipoprotein cholesterol (P = .03), insulin level (P = .01), and homeostasis model assessment index (P = .02) had significant changes in the metformin group. At the end of the intervention, 8 patients (28.57{\%}) lost more than 7{\%} of their body weight in the metformin group. Mean body weight returned to baseline after patients stopped the intervention in the metformin group. Conclusions: Metformin can significantly reduce body weight and reverse metabolic abnormalities in clozapine-treated patients with schizophrenia and preexisting metabolic abnormalities. However, the beneficial effects of metformin on body weight disappeared after discontinuing this medication. Trial Registration: ClinicalTrials.gov identifier: NCT01300637.",
author = "Chen, {Chun Hsin} and Huang, {Ming Chyi} and Kao, {Chung Feng} and Lin, {Shih Ku} and Kuo, {Po Hsiu} and Chiu, {Chih Chiang} and Lu, {Mong Liang}",
year = "2013",
doi = "10.4088/JCP.12m08186",
language = "English",
volume = "74",
journal = "Journal of Clinical Psychiatry",
issn = "0160-6689",
publisher = "Physicians Postgraduate Press Inc.",
number = "5",

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T1 - Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight

T2 - A 24-week, randomized, double-blind, placebo-controlled study

AU - Chen, Chun Hsin

AU - Huang, Ming Chyi

AU - Kao, Chung Feng

AU - Lin, Shih Ku

AU - Kuo, Po Hsiu

AU - Chiu, Chih Chiang

AU - Lu, Mong Liang

PY - 2013

Y1 - 2013

N2 - Objective: Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia. Whether or not the beneficial effects can be sustained after discontinuation of metformin needs to be evaluated. We conducted a 24-week randomized, double-blind, placebo-controlled study to evaluate the effect of metformin on metabolic features in clozapine-treated patients with schizophrenia and followed their body weight after stopping the intervention for at least 24 weeks. Method: The study was conducted between September 2008 and July 2011. We recruited patients with DSM-IV diagnosis of schizophrenia or schizoaffective disorder who had been taking clozapine for more than 3 months, were overweight or obese, or fulfilled at least 1 criteria of metabolic syndrome. Eligible patients were randomized to receive metformin 1,500 mg/d or placebo. We followed metabolic features at baseline and at weeks 2, 4, 8, 16, and 24 and rechecked body weight when the patients stopped the trial after at least 24 weeks. Results: A total of 55 subjects (28 in the metformin and 27 in the placebo group) were enrolled. There were no significant differences in all baseline characteristics between the 2 groups, except that patients in the metformin group had higher fasting plasma glucose levels (P = .03). After the 24-week intervention, body weight (P <.0001), body mass index (P <.0001), fasting plasma glucose (P <.0001), high-density lipoprotein cholesterol (P = .03), insulin level (P = .01), and homeostasis model assessment index (P = .02) had significant changes in the metformin group. At the end of the intervention, 8 patients (28.57%) lost more than 7% of their body weight in the metformin group. Mean body weight returned to baseline after patients stopped the intervention in the metformin group. Conclusions: Metformin can significantly reduce body weight and reverse metabolic abnormalities in clozapine-treated patients with schizophrenia and preexisting metabolic abnormalities. However, the beneficial effects of metformin on body weight disappeared after discontinuing this medication. Trial Registration: ClinicalTrials.gov identifier: NCT01300637.

AB - Objective: Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia. Whether or not the beneficial effects can be sustained after discontinuation of metformin needs to be evaluated. We conducted a 24-week randomized, double-blind, placebo-controlled study to evaluate the effect of metformin on metabolic features in clozapine-treated patients with schizophrenia and followed their body weight after stopping the intervention for at least 24 weeks. Method: The study was conducted between September 2008 and July 2011. We recruited patients with DSM-IV diagnosis of schizophrenia or schizoaffective disorder who had been taking clozapine for more than 3 months, were overweight or obese, or fulfilled at least 1 criteria of metabolic syndrome. Eligible patients were randomized to receive metformin 1,500 mg/d or placebo. We followed metabolic features at baseline and at weeks 2, 4, 8, 16, and 24 and rechecked body weight when the patients stopped the trial after at least 24 weeks. Results: A total of 55 subjects (28 in the metformin and 27 in the placebo group) were enrolled. There were no significant differences in all baseline characteristics between the 2 groups, except that patients in the metformin group had higher fasting plasma glucose levels (P = .03). After the 24-week intervention, body weight (P <.0001), body mass index (P <.0001), fasting plasma glucose (P <.0001), high-density lipoprotein cholesterol (P = .03), insulin level (P = .01), and homeostasis model assessment index (P = .02) had significant changes in the metformin group. At the end of the intervention, 8 patients (28.57%) lost more than 7% of their body weight in the metformin group. Mean body weight returned to baseline after patients stopped the intervention in the metformin group. Conclusions: Metformin can significantly reduce body weight and reverse metabolic abnormalities in clozapine-treated patients with schizophrenia and preexisting metabolic abnormalities. However, the beneficial effects of metformin on body weight disappeared after discontinuing this medication. Trial Registration: ClinicalTrials.gov identifier: NCT01300637.

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