title: Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02751307.
authors.affiliation: Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.|Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Chiu
authors.affiliation: Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.|Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Mong-Liang
authors.initials: ML
authors.lastname: Lu
authors.affiliation: Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.|Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Chyi
authors.initials: MC
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.|Graduate Institute of Medical Science, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Po-Yu
authors.initials: PY
authors.lastname: Chen
authors.affiliation: Biostatistics Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yen-Kuang
authors.initials: YK
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.|Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shih-Ku
authors.initials: SK
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.|Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chun-Hsin
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D003024:Clozapine / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D007004:Hypoglycemic Agents; D008687:Metformin; D003024:Clozapine