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Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study

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  • Chih-Chiang Chiu
  • Mong-Liang Lu
  • Ming-Chyi Huang
  • Po-Yu Chen
  • Yen-Kuang Lin
  • Shih-Ku Lin
  • Chun-Hsin Chen

Abstract

Background: Metformin has been used for alleviating metabolic abnormalities in patients with schizophrenia. The lowest dose of metformin to treat metabolic abnormalities in clozapine-treated patients is 1000 mg/d. This study was designed to determine whether metformin at 500 mg/d and 1000 mg/d is effective in improving the metabolic profiles of clozapine-treated patients with pre-existing metabolic abnormalities, and whether its effectiveness depends on metformin dosage. Methods: In this 12-week, randomized, double-blind, placebo-controlled trial, metformin at 500 mg/d or 1000 mg/d was prescribed to clozapine-treated patients with schizophrenia who had pre-existing metabolic abnormalities. The recruited patients underwent physical and laboratory evaluations at weeks 4, 8, and 12. The outcomes were any changes in metabolic traits. Results: Among the 96 clozapine-treated patients with schizophrenia screened for the trial, 55 patients with pre-existing metabolic abnormalities were randomly assigned to placebo (n = 18), metformin dosage at 500 mg/d (n = 18), and metformin dosage at 1000 mg/d (n = 19) groups. The body weight (BW) of patients in the metformin 1000 mg/d group significantly decreased, by a mean of 0.97 kg over the 12 week trial period. Moreover, patients in the metformin at 500 mg/d and 1000 mg/d groups had a significant decrease in body mass index (BMI) after 12 weeks, with the mean decrease being 0.70 and 0.50 kg/m2, respectively. No significant changes were observed in the other metabolic parameters of patients in the three groups. Conclusions: Our results demonstrated that a low metformin dosage of either 500 mg/d or 1000 mg/d for 12 weeks slightly reduced the BW and BMI of clozapine-treated patients with pre-existing metabolic abnormalities. A longer period of treatment with a larger sample is warranted to determine the factors that influence the metformin treatment response. Trial Registration: ClinicalTrials.gov NCT02751307

Suggested Citation

  • Chih-Chiang Chiu & Mong-Liang Lu & Ming-Chyi Huang & Po-Yu Chen & Yen-Kuang Lin & Shih-Ku Lin & Chun-Hsin Chen, 2016. "Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study," PLOS ONE, Public Library of Science, vol. 11(12), pages 1-12, December.
    • Handle: RePEc:plo:pone00:0168347
    DOI: 10.1371/journal.pone.0168347
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    1. Dan J Siskind & Janni Leung & Anthony W Russell & Daniel Wysoczanski & Steve Kisely, 2016. "Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-15, June.
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