Efficacy of Metformin Treatment with Respect to Weight Reduction in Children and Adults with Obesity: A Systematic Review
Obesity and its related complications are increasing health issues. Since generally only minor weight loss is obtained with lifestyle intervention, additional pharmacological therapies such as metformin are often used.
We conducted a systematic review to provide an overview of the efficacy of ≥ 6 months of metformin treatment in children and adults with respect to weight, insulin resistance, and progression toward type 2 diabetes mellitus (T2DM).
In September 2018, we searched PubMed, Embase, and the Cochrane Library for studies published in English using the keywords metformin, obesity/overweight, and weight loss. Prospective studies reporting weight/body mass index (BMI) as a primary or secondary outcome in patients with overweight/obesity with ≥ 6 months’ metformin treatment were included. Included subjects were children and adults with overweight/obesity who received ≥ 6 months of metformin and/or lifestyle intervention, and/or placebo and/or lifestyle intervention, and/or standard care. Studies were independently screened by two reviewers. Data were extracted by one and verified by the other reviewer, and both reviewers assessed the risk of bias using the Cochrane risk-of-bias tool.
Our review includes 15 pediatric and 14 adult studies. In children, after 6 months, more than half the studies reported a greater reduction in BMI with metformin versus controls. Only six studies had an intervention of > 6 months, and these studies found no further improvement in BMI in the metformin users, though their BMI was lower than that of controls. Three studies showed a significant improvement in insulin sensitivity in the metformin versus the control group. Adults using metformin experienced and maintained small decreases in weight irrespective of duration of intervention. In 11 of 14 studies, a greater reduction in weight/BMI was observed with metformin than with placebo. Progression toward T2DM was significantly reduced in adults using metformin, ranging from 7 to 31%. The safety and tolerability of metformin, withdrawal of participants, and comparison with other drugs were not taken into account.
The effects of metformin on weight/BMI vary, with smaller reductions in children than in adults. This could be because of differences in adherence, daily dosage, and insulin status. Metformin significantly reduced the progression toward T2DM in adults. Therefore, metformin should be considered as a treatment for obesity and its related complications.
Compliance with Ethical Standards
Conflict of interest
Y. Lentferink, C. Knibbe, and M. van der Vorst have no conflicts of interest that are directly relevant to the content of this article.
This article does not contain any studies with human participants or animals performed by any of the authors. Formal consent was not required for this type of study.
No sources of funding were used to conduct this study or prepare this manuscript.
- 1.NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627–42.CrossRefGoogle Scholar
- 3.World Health Organisation, Obesity and overweight. 2017;2018(May).Google Scholar
- 16.National Institute of Diabetes and Digestive and Kidney Diseases. Prescription medications to treat overweight and obesity. 2016;2018(May).Google Scholar
- 28.Higgins JPT, Altman DG, Sterne JAC (editors), Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Altman DG, Sterne JAC (editors), Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, 2011.Google Scholar
- 40.Warnakulasuriya LS, Fernando MMA, Adikaram AVN, et al., Metformin in the management of childhood obesity: a randomized control trial. Child Obes 2018.Google Scholar
- 41.Wilson DM, Abrams SH, Aye T, et al. Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up. Arch Pediatr Adolesc Med. 2010;164(2):116–23.Google Scholar
- 54.Electronic Medicines Compendium, Metformin. 2017;2018(May).Google Scholar
- 56.van Rongen A, van der Aa MP, Matic M, et al.. Increased metformin clearance in overweight and obese adolescents: a Pharmacokinetic substudy of a randomized controlled trial. Paediatr Drugs. 2018.Google Scholar