The role of metformin in treatment of weight gain associated with atypical antipsychotic treatment in children and adolescents: A systematic review and meta-analysis of randomized controlled trials

Abstract

IntroductionSecond-generation antipsychotics are associated with significant weight gain. The aim of this systematic review and meta-analysis was to determine the efficacy and safety of metformin for the treatment of weight gain in children and young adults treated with second-generation antipsychotics.MethodsWe followed PRISMA guidelines to evaluated studies published before March 2020 in Medline, Google Scholar, PubMed, Cochrane library database, annual scientific sessions of the American Psychiatric Association, American Academy of Child and Adolescent, Psychiatry, and American Society of Clinical Psychopharmacology. Studies included compared metformin with the placebo for management of weight gain in children and adolescents taking atypical antipsychotics. Non-randomized studies, animal experiment studies, editorials, and review studies were excluded. Multiple parameters, including change in anthropometric-biochemical parameters, drug discontinuation rate, and side effects among the groups were assessed. The random-effects method was used for meta-analysis.ResultsFour studies with were included in the final analysis (213 patients; metformin: 106; control: 107). After pooled analysis, 12–16 weeks of metformin therapy was associated with a significant reduction in weight [(mean difference (MD): −4.53 lbs, confidence interval (CI): −6.19 to −2.87, p-value < 0.001)], and BMI z score [MD, −0.09, CI: −0.16, −0.03, p-value: 0.004] compared to control. Metformin was also associated with a significant reduction in insulin resistance [MD: −1.38, CI: −2.26 to −0.51, p-value: 0.002]. There were higher odds of nausea-vomiting [OR: 4.07, CI: 1.32–12.54, p-value: 0.02] and diarrhea [OR: 2.93, CI: 1.50–5.71, p-value: 0.002] in the metformin group. However, there was no difference in drug discontinuation rate [OR: 1.45, CI: 0.41–5.06, p-value: 0.56].ConclusionMetformin may prove beneficial in the treatment of weight gain in children treated with second-generation antipsychotics. The pooled treatment effect showed a significant reduction in BMI Z-score and weight in just 12–16 weeks. The limitations include small sample size, variation in metformin dose, and duration of treatment. This meta-analysis should be interpreted as promising, and further larger studies are warranted before drawing a conclusion.

Efficacy of topiramate in reducing second‐generation antipsychotic‐associated weight gain among children: A systematic review and meta‐analysis

“…A previous meta‐analysis assessed the efficacy and safety of metformin in reducing weight secondary to antipsychotic use in children 52 . While this study reported a 2 kg weight reduction when taking metformin, along with a statistically significant reduction in BMI z‐score, it is notable that, like topiramate, metformin did not significantly impact metabolic outcomes such as triglyceride, total cholesterol, LDL, HDL, and blood sugar levels.…”

Clinical assessment of liraglutide use in prediabetic and obese schizophrenic patients: A systematic literature review and meta-analysis

“…There are other known pharmacological strategies that have been tried as add-on to adipogenic antipsychotics and are still used in clinical practice, e.g., Metformin, which is an anti-diabetic drug that has proven e cacy in wight loss among patients who take antipsychotics and suffer weight gain (41,42). The use of metformin as adjunctive therapy to treat weight gain was implemented when non-pharmacological treatment failed.…”