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Review | Comparative Effectiveness Research

Systematic Review of the Benefits and Risks of Metformin in Treating Obesity in Children Aged 18 Years and Younger

Marian S. McDonagh, PharmD1; Shelley Selph, MD1; Alp Ozpinar, BS2; Carolyn Foley, BA2
[+] Author Affiliations
1Department of Medical Informatics and Clinical Epidemiology, School of Medicine, Oregon Health & Science University, Portland, Oregon
2School of Medicine, Oregon Health & Science University, Portland, Oregon
JAMA Pediatr. 2014;168(2):178-184. doi:10.1001/jamapediatrics.2013.4200.
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Importance  Childhood obesity is an important public health problem with increasing prevalence. Because treatment often has limited success, new approaches must be identified.

Objective  To evaluate the effectiveness and safety of metformin for treating obesity in children aged 18 years and younger without a diagnosis of diabetes mellitus.

Evidence Review  We included randomized clinical trials identified through searches of MEDLINE, the Cochrane Library, and ClinicalTrials.gov. Our primary outcome measure was change in body mass index (BMI, calculated as weight in kilograms divided by height in meters squared). We assessed study quality, pooled data using a random-effects model, and performed subgroup and sensitivity analyses.

Findings  Fourteen randomized clinical trials were eligible. For BMI, moderate-strength evidence indicated a reduction of −1.38 (95% CI, −1.93 to −0.82) from baseline compared with control at 6 months. A similar, if less dramatic, effect was observed in studies less than 6 months, but the pooled estimate from studies of 1 year of treatment was not statistically significant. Subgroup analyses indicated smaller, but significant, effects for those with baseline BMI below 35, those of Hispanic ethnicity, those with acanthosis nigricans, those who had tried and failed diet and exercise programs, and in studies with more girls or higher mean age (adolescents). Moderate-strength evidence indicated that with metformin, 26% reported a gastrointestinal event compared with 13% in control groups (relative risk, 2.05; 95% CI, 1.19-3.54), although there was no difference in discontinuations due to adverse events. No serious adverse events were reported.

Conclusions and Relevance  Metformin provides a statistically significant, but very modest reduction in BMI when combined with lifestyle interventions over the short term. A large trial is needed to determine the benefits to subgroups or impacts of confounders. In the context of other options for treating childhood obesity, metformin has not been shown to be clinically superior.

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Figure 1.
Results of Literature Search
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Figure 2.
Change in Body Mass Index With Metformin Compared With Control by Length of Follow-up

Body mass index is calculated as weight in kilograms divided by height in meters squared.

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Figure 3.
Funnel Plot for Change in Body Mass Index
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Figure 4.
Change in Total Cholesterol After Metformin Treatment
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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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