Metformin for Weight Gain and Metabolic Abnormalities Associated With Antipsychotic Treatment

Abstract

This meta-analysis examined the effectiveness and safety of metformin to prevent or treat weight gain and metabolic abnormalities associated with antipsychotic drugs. We systematically searched in both English- and Chinese-language databases for metformin randomized controlled clinical trials (RCTs) using placebo in patients taking antipsychotics. Twenty-one RCTs (11 published in English and 10 in Chinese) involving 1547 subjects (778 on metformin, 769 on placebo) were included in this meta-analysis. Metformin was significantly superior to placebo (standard mean differences, -0.69 to -0.51; P = 0.01-0.0001) in the primary outcome measures (body weight, body mass index, fasting glucose, fasting insulin, triglycerides, and total cholesterol). Metformin was significantly superior to placebo in some secondary outcome measures but not in others. Significantly higher frequencies of nausea/vomiting and diarrhea were found in the metformin group, but no differences were found in other adverse drug reactions. In the metformin group, the frequency of nausea/vomiting was 14%, and of diarrhea, 7%. Subgroup and sensitivity analyses demonstrated that primary outcomes were influenced by ethnicity, treatment style (intervention vs prevention), metformin dose, study duration, and mean age. Body weight standard mean difference was -0.91 (confidence interval [CI], -1.40 to -0.41) in 3 prevention RCTs in naive patients, -0.66 (CI, -1.02 to -0.30) in 5 intervention RCTs during the first year, and -0.50 (CI, -0.73 to -0.27) in 9 intervention RCTs in chronic patients. This meta-analysis suggests that adjunctive metformin is an effective, safe, and reasonable choice for antipsychotic-induced weight gain and metabolic abnormalities.

Commentary: A Randomized, Double-Blind, Placebo-Controlled Trial of Metformin Treatment of Weight Gain Associated with Initiation of Atypical Antipsychotic Therapy in Children and Adolescents

“…These include its ability to decrease insulin resistance (reversing the insulin resistance caused by antipsychotics) and reduce hepatic glucose production (11, 12). While multiple RCTs and meta-analyses show metformin to be moderately beneficial for promoting weight loss in adults using antipsychotics, others found no weight loss benefits (13–15). The weight-reducing potential of metformin in non-diabetic, overweight children, and adolescents has been previously demonstrated (16).…”

Glucagon‐like peptide‐1 receptor agonists for antipsychotic‐associated cardio‐metabolic risk factors: A systematic review and individual participant data meta‐analysis

“…Orlistat is associated with poor adherence because of steatorrhoea . Finally, there is only modest (and heterogeneous) body weight loss following the addition of metformin or topiramate for obese and overweight patients on antipsychotics and/or those at risk for antipsychotic body weight gain …”

Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study

“…Metformin has previously been shown to have no effect on psychiatric symptoms in antipsychotic-treated patients [23] or clozapine-treated patients [12]. The patients in the current study had used clozapine for more than three months before being enrolled in the study, but the exact duration of clozapine use was unknown.…”