Efficacy and Safety of Metformin for Obesity: A Systematic Review

Abstract

CONTEXT: The efficacy and safety of metformin for obesity in children and adolescents remains unclear. OBJECTIVE: To assess the efficacy and safety of metformin via systematic review. DATA SOURCES: Data sources included PubMed, Embase, the Cochrane Library, Scopus, and ClincalTrials.gov (inception to November 2019). STUDY SELECTION: We selected randomized controlled trials (RCTs) in which researchers assessed the efficacy and safety of metformin with lifestyle interventions, compared with a placebo with lifestyle interventions, in children and adolescents with obesity. DATA EXTRACTION: Two researchers independently extracted data and assessed quality. The primary outcomes were mean changes from baseline in BMI, BMI z score, homeostatic model assessment of insulin resistance, and gastrointestinal adverse effects. RESULTS: Twenty-four RCTs (1623 patients; range: 16 to 151) were included. Ages ranged from 4 to 19 years, and follow-up ranged from 2 months to 2 years. Metformin resulted in a modest decrease in BMI (range of mean values: −2.70 to 1.30 vs −1.12 to 1.90), BMI z score (range of mean values: −0.37 to −0.03 vs −0.22 to 0.15), and homeostatic model assessment of insulin resistance (range of mean values: −3.74 to 1.00 vs −1.40 to 2.66). Metformin resulted in a higher frequency of gastrointestinal adverse effects (range: 2% to 74% vs 0% to 42%). LIMITATIONS: The available evidence is of varying quality, with high heterogeneity between trials, suggesting some uncertainty in the benefits of metformin in this population. CONCLUSIONS: With this systematic review of RCTs, we suggest that metformin has modest but favorable effects on weight and insulin resistance and a tolerable safety profile among children and adolescents with obesity.

Metabolomic Approaches to Investigate the Effect of Metformin: An Overview

“…Pharmacokinetically, metformin does not undergo hepatic metabolism, so it is considered safe from a hepatic standpoint, and metformin-induced hepatotoxicity is very rare, with less than 20 cases having been described over several decades [7]. Various clinical studies also supported the safety and tolerability of metformin treatment [8][9][10]. Thus, metformin has been used for almost 70 years to treat T2DM patients with its safety and clinical usefulness.…”

Protective Effects of Individual and Combined Low Dose Beta-Carotene and Metformin Treatments against High-Fat Diet-Induced Responses in Mice

“…Doses clinically used for this purpose range from 1000 to 2500 mg/day, where 2000 mg/day may represent the optimal dose for most patients [ 21 ]. MET is receiving increasing attention in recent years as a potential anti-obesity drug on the basis of clinical and animal studies [ 22 , 23 , 24 , 25 ]. MET-induced bodyweight loss is mainly attributed to decreased caloric intake, resulting from direct and indirect (gut–brain axis mediated) effects of the drug on central circuitries controlling appetite [ 25 ].…”

Is autosomal dominant polycystic kidney disease an early sweet disease?

“…Lactate acidosis, a rare but alarming side effect of metformin, mainly occurs in patients with kidney, hepatic, or cardiac insufficiency [73]. In the pediatric population, metformin has been reported to improve insulin sensitivity and weight loss in obese children and adolescents [74]. In a recent pilot study, a low dose of metformin (850 mg/ day) in young children with obesity and risk markers for metabolic syndrome was well tolerated and had a positive effect on body composition and inflammatory markers after 12 months [75].…”