Metformin addition attenuates olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients: a double-blind, placebo-controlled study.
OBJECTIVE
The purpose of this study was to assess the efficacy of metformin in preventing olanzapine-induced weight gain.


METHODS
Forty patients with schizophrenia were randomly assigned to treatment for 12 weeks with olanzapine, 15 mg/day, plus metformin, 750 mg/day (N=20), or olanzapine, 15 mg/day, plus placebo (N=20). This investigation was conducted in a double-blind fashion. Planned assessments included body weight, body mass index, proportion of patients who gained more than 7% of their baseline weight at the end of the 12-week treatment, waist circumference, waist-to-hip ratio, fasting glucose and insulin, insulin resistance index, and scores on the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS).


RESULTS
Of the 40 patients who were randomly assigned, 37 (92.5%) completed treatments. The weight, body mass index, waist circumference, and waist-to-hip ratio levels increased less in the olanzapine plus metformin group relative to the olanzapine plus placebo group during the 12-week follow-up period. The insulin and insulin resistance index values of the olanzapine plus placebo group increased significantly at weeks 8 and 12. In contrast, the insulin and insulin resistance index levels of the olanzapine plus metformin group remained unchanged. Significantly fewer patients in the olanzapine plus metformin group relative to patients in the olanzapine plus placebo group increased their baseline weight by more than 7%, which was the cutoff for clinically meaningful weight gain. There was a significant decrease in SAPS and SANS scores within each group from baseline to week 12, with no between-group differences. Metformin was tolerated well by all patients.


CONCLUSIONS
Metformin was effective and safe in attenuating olanzapine-induced weight gain and insulin resistance in drug-naive first-episode schizophrenia patients. Patients displayed good adherence to this type of preventive intervention.
Wu
Ren-Rong
RR
Institute of Mental Health of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhao
Jing-Ping
JP
Guo
Xiao-Feng
XF
He
Yi-Qun
YQ
Fang
Mao-Sheng
MS
Guo
Wen-Bin
WB
Chen
Jin-Dong
JD
Li
Le-Hua
LH
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D015992:Body Mass Index; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000139:chemically induced / Q000517:prevention & control*; D000077152:Olanzapine; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D049629:Waist-Hip Ratio; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D007004:Hypoglycemic Agents; D010919:Placebos; D001569:Benzodiazepines; D008687:Metformin; D000077152:Olanzapine