Efficacy of metformin for treatment and prevention of antipsychotic-induced overweight and obesity in women: an open-label, randomized, prospective placebo-controlled study

Background: The prevalence of obesity and metabolic abnormalities is increased patients with mental disorders receiving psychopharmacotherapy, which significantly impairs their treatment adherence. Aims: To evaluate the efficacy and safety of metformin in prevention and treatment obesity and overweight in patients with mental disorders receiving antipsychotics. Materials and methods : This was an open-label, prospective, randomized, placebo-controlled study of female patients with mental disorders (age, 18 to 50). The patients were randomized into two groups in a 2:1 ratio: the treatment group received metformin and the control group received placebo. Metformin was administered at a starting dose of 500 mg daily, with subsequent up-titration every 2 weeks when necessary, up to 2000 mg daily. The treatment duration was 6 months. Results: Baseline BMI in the treatment group (N=62) was 27,3 [24,0; 30,4] kg/m 2 ; it decreased to 26,0 [22,5; 30,5] kg/m 2 , p < 0.0001, Wilсoxon test) after 6 months of treatment. The patients receiving metformin decreased their body weight by 3 [-6; 0] kg, or -4,0 [-8; 0] %. In the placebo group (N=30), the baseline BMI was 27,5 [24,0; 32,0] kg/m 2 and increased to 28,2 [25,8; 34,0] kg/m 2 at 6 month (p=0.001, Wilсoxon test), or 3 [1; 6] kg. After 6 months of treatment, the difference in BMI between the metformin and placebo groups was significant (26,0 и 28,2 kg/m 2 , respectively, р=0,027, Mann-Withney test). Six (6) of 62 patients treated with metformin had side effects and were switched to an equivalent dose of prolonged release metformin, with reduction of side effects in 5 of them. Conclusions: The use of metformin in patients with mental disorders receiving antipsychotics allows for reduction or stabilization of body weight in 80% of cases, with ≥5% decrease of body weight in 44% of patients. It is recommended to start metformin at a dose of 500 mg daily with subsequent up-titration of up to 2000 mg if necessary.