Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain: a randomized controlled trial

JAMA. 2008 Jan 9;299(2):185-93. doi: 10.1001/jama.2007.56-b.


Context: Weight gain, a common adverse effect of antipsychotic medications, is associated with medical comorbidities in psychiatric patients.

Objective: To test the efficacy of lifestyle intervention and metformin alone and in combination for antipsychotic-induced weight gain and abnormalities in insulin sensitivity.

Design, setting, and patients: A randomized controlled trial (October 2004-December 2006) involving 128 adult patients with schizophrenia in the Mental Health Institute of the Second Xiangya Hospital, Central South University, China. Participants who gained more than 10% of their predrug weight were assigned to 1 of 4 treatment groups.

Interventions: Patients continued their antipsychotic medication and were randomly assigned to 12 weeks of placebo, 750 mg/d of metformin alone, 750 mg/d of metformin and lifestyle intervention, or lifestyle intervention only.

Main outcome measures: Body mass index, waist circumference, insulin levels, and insulin resistance index.

Results: All 128 first-episode schizophrenia patients maintained relatively stable psychiatric improvement. The lifestyle-plus-metformin group had mean decreases in body mass index (BMI) of 1.8 (95% confidence interval [CI], 1.3-2.3), insulin resistance index of 3.6 (95% CI, 2.7-4.5), and waist circumference of 2.0 cm (95% CI, 1.5-2.4 cm). The metformin-alone group had mean decreases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 3.5 (95% CI, 2.7-4.4), and waist circumference of 1.3 cm (95% CI, 1.1-1.5 cm). The lifestyle-plus-placebo group had mean decreases in BMI of 0.5 (95% CI, 0.3-0.8) and insulin resistance index of 1.0 (95% CI, 0.5-1.5). However, the placebo group had mean increases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 0.4 (95% CI, 0.1-0.7), and waist circumference of 2.2 cm (95% CI, 1.7-2.8 cm). The lifestyle-plus-metformin treatment was significantly superior to metformin alone and to lifestyle plus placebo for weight, BMI, and waist circumference reduction.

Conclusions: Lifestyle intervention and metformin alone and in combination demonstrated efficacy for antipsychotic-induced weight gain. Lifestyle intervention plus metformin showed the best effect on weight loss. Metformin alone was more effective in weight loss and improving insulin sensitivity than lifestyle intervention alone. Trial Registration Identifier: NCT00451399.

Publication types

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

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects*
  • Blood Glucose
  • Body Mass Index
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance
  • Male
  • Metformin / therapeutic use*
  • Overweight / chemically induced*
  • Overweight / prevention & control
  • Risk Reduction Behavior*
  • Schizophrenia / drug therapy
  • Weight Gain / drug effects*
  • Weight Loss


  • Antipsychotic Agents
  • Blood Glucose
  • Hypoglycemic Agents
  • Metformin

Associated data