Lifestyle Intervention and Metformin for Treatment of Antipsychotic-Induced Weight Gain

TLDR

Weight gain, a common adverse effect of antipsychotic medications, is associated with medical comorbidities in psychiatric patients. The study tested the efficacy of lifestyle intervention, metformin alone, and their combination for antipsychotic‑induced weight gain and insulin sensitivity abnormalities. In a 12‑week randomized controlled trial of 128 schizophrenia patients, participants who gained >10% pre‑drug weight were assigned to placebo, 750 mg/d metformin, metformin plus lifestyle intervention, or lifestyle intervention alone, with outcomes measured by BMI, waist circumference, insulin levels, and insulin resistance index. The combination of lifestyle intervention and metformin produced the greatest reductions in BMI, waist circumference, and insulin resistance, outperforming metformin alone and lifestyle alone, while the placebo group experienced weight gain. Trial registered at clinicaltrials.gov (NCT00451399).

Abstract

Weight gain, a common adverse effect of antipsychotic medications, is associated with medical comorbidities in psychiatric patients.To test the efficacy of lifestyle intervention and metformin alone and in combination for antipsychotic-induced weight gain and abnormalities in insulin sensitivity.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.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.Body mass index, waist circumference, insulin levels, and insulin resistance index.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.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 clinicaltrials.gov Identifier: NCT00451399.