Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial

Schizophr Res. 2007 Jul;93(1-3):99-108. doi: 10.1016/j.schres.2007.03.029. Epub 2007 May 8.


Background: Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables.

Methods: Eighty patients taking olanzapine (5-20 mg daily for more than 4 consecutive months) were randomly allocated to metformin (n=40; 850 to 2550 mg daily) or placebo (n=40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment.

Results: The metformin group lost 1.4+/-3.2 kg (p=0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: -0.18+/-2.8 kg (p=0.7). The HOMA-IR significantly increased after placebo (p=0.006) and did not change after metformin (p=0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels.

Conclusions: Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Bipolar Disorder / blood
  • Bipolar Disorder / drug therapy*
  • Blood Glucose / metabolism
  • Body Mass Index
  • Body Weight / drug effects*
  • Brief Psychiatric Rating Scale
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Energy Metabolism / drug effects
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin Resistance / physiology*
  • Leptin / blood
  • Lipids / blood
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Olanzapine
  • Schizophrenia / blood
  • Schizophrenia / drug therapy*
  • Statistics as Topic


  • Antipsychotic Agents
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Leptin
  • Lipids
  • Benzodiazepines
  • Metformin
  • Olanzapine