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University of Groningen Drug Interventions for the Treatment Of University of Groningen Drug interventions for the treatment of obesity in children and adolescents Mead, Emma; Atkinson, Greg; Richter, Bernd; Metzendorf, Maria-Inti; Baur, Louise; Finer, Nicholas; Corpeleijn, Eva; O'Malley, Claire; Ells, Louisa J. Published in: Cochrane database of systematic reviews (Online) DOI: 10.1002/14651858.CD012436 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2016 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Mead, E., Atkinson, G., Richter, B., Metzendorf, M-I., Baur, L., Finer, N., Corpeleijn, E., O'Malley, C., & Ells, L. J. (2016). Drug interventions for the treatment of obesity in children and adolescents. Cochrane database of systematic reviews (Online), (11), [012436]. https://doi.org/10.1002/14651858.CD012436 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 26-09-2021 Cochrane Database of Systematic Reviews Drug interventions for the treatment of obesity in children and adolescents (Review) Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, Corpeleijn E, O’Malley C, Ells LJ Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, Corpeleijn E, O’Malley C, Ells LJ. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database of Systematic Reviews 2016, Issue 11. Art. No.: CD012436. DOI: 10.1002/14651858.CD012436. www.cochranelibrary.com Drug interventions for the treatment of obesity in children and adolescents (Review) Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 7 OBJECTIVES ..................................... 9 METHODS ...................................... 9 Figure1. ..................................... 11 RESULTS....................................... 14 Figure2. ..................................... 18 Figure3. ..................................... 19 Figure4. ..................................... 26 Figure5. ..................................... 27 DISCUSSION ..................................... 27 AUTHORS’CONCLUSIONS . 29 ACKNOWLEDGEMENTS . 30 REFERENCES ..................................... 30 CHARACTERISTICSOFSTUDIES . 44 DATAANDANALYSES. 118 Analysis 1.1. Comparison 1 Body mass index (BMI): pharmacological interventions versus comparators, Outcome 1 ChangeinBMI(alltrials). 120 Analysis 1.2. Comparison 1 Body mass index (BMI): pharmacological interventions versus comparators, Outcome 2 ChangeinBMI(drugtype).. 121 Analysis 1.3. Comparison 1 Body mass index (BMI): pharmacological interventions versus comparators, Outcome 3 ChangeinBMI(dropoutrate).. 122 Analysis 1.4. Comparison 1 Body mass index (BMI): pharmacological interventions versus comparators, Outcome 4 Change in BMI (intention-to-treat (ITT) analysis). .......... 124 Analysis 1.5. Comparison 1 Body mass index (BMI): pharmacological interventions versus comparators, Outcome 5 ChangeinBMI(funding). 125 Analysis 1.6. Comparison 1 Body mass index (BMI): pharmacological interventions versus comparators, Outcome 6 Change in BMI (publication date). 127 Analysis 1.7. Comparison 1 Body mass index (BMI): pharmacological interventions versus comparators, Outcome 7 ChangeinBMI(qualityoftrial). 128 Analysis 1.8. Comparison 1 Body mass index (BMI): pharmacological interventions versus comparators, Outcome 8 ChangeinBMI(country). 129 Analysis 1.9. Comparison 1 Body mass index (BMI): pharmacological interventions versus comparators, Outcome 9 ChangeinBMI(meanage).. 130 Analysis 2.1. Comparison 2 Weight: pharmacological interventions versus comparators, Outcome 1 Change in weight (all trials). .................................... 131 Analysis 2.2. Comparison 2 Weight: pharmacological interventions versus comparators, Outcome 2 Change in weight (drugtype). .................................. 132 Analysis 3.1. Comparison 3 Adverse effects: pharmacological interventions versus comparator, Outcome 1 Serious adverse events. .................................... 133 Analysis 3.2. Comparison 3 Adverse effects: pharmacological interventions versus comparator, Outcome 2 Discontinued trialbecauseofadverseevents. 134 ADDITIONALTABLES. 135 APPENDICES ..................................... 150 WHAT’SNEW..................................... 234 CONTRIBUTIONSOFAUTHORS . 235 DECLARATIONSOFINTEREST . 235 SOURCESOFSUPPORT . 235 Drug interventions for the treatment of obesity in children and adolescents (Review) i Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. DIFFERENCES BETWEEN PROTOCOL AND REVIEW . .... 236 NOTES........................................ 236 INDEXTERMS .................................... 236 Drug interventions for the treatment of obesity in children and adolescents (Review) ii Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Drug interventions for the treatment of obesity in children and adolescents Emma Mead1, Greg Atkinson1, Bernd Richter2, Maria-Inti Metzendorf2, Louise Baur3, Nicholas Finer4, Eva Corpeleijn5, Claire O’Malley6, Louisa J Ells1 1Health and Social Care Institute, Teesside University, Middlesbrough, UK. 2Cochrane Metabolic and Endocrine Disorders Group, Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. 3Department of Paediatrics and Child Health, The University of Sydney, Westmead, Australia. 4National Centre for Cardiovascular Prevention and Outcomes, UCL Institute of Cardiovascular Science, London, UK. 5Department of Epidemiology, University Medical Centre Groningen, Groningen, Netherlands. 6School of Medicine, Pharmacy and Health, Durham University Queen’s Campus, Stockton- on-Tees, UK Contact address: Emma Mead, Health and Social Care Institute, Teesside University, Middlesbrough, TS1 3BA, UK. [email protected], [email protected]. Editorial group: Cochrane Metabolic and Endocrine Disorders Group. Publication status and date: New, published in Issue 11, 2016. Citation: Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, Corpeleijn E, O’Malley C, Ells LJ. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database of Systematic Reviews 2016, Issue 11. Art. No.: CD012436. DOI: 10.1002/14651858.CD012436. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences. Objectives To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents. Search methods We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016. We checked references and applied no language restrictions. Selection criteria We selected randomised controlled trials (RCTs) of pharmacological interventions for treating obesity (licensed and unlicensed for this indication) in children and adolescents (mean age under 18 years) with or without support of family members, with a minimum of three months’ pharmacological intervention and six months’ follow-up from baseline. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. In addition, we excluded trials which included growth hormone therapies and pregnant participants. Data collection and analysis Two review authors independently assessed trial quality and extracted data following standard Cochrane methodology. Where necessary we contacted authors for additional information. Drug interventions for the treatment of obesity in children and adolescents (Review) 1 Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Main results We included 21 trials and identified eight ongoing trials. The included trials evaluated metformin (11 trials), sibutramine (six trials), orlistat (four trials), and one trial arm investigated the combination of metformin and fluoxetine. The ongoing trials evaluated metformin (four trials), topiramate (two trials) and exenatide (two trials). A total of 2484 people participated in the included trials, 1478 participants were randomised to drug intervention and 904 to comparator groups (91 participants took part in two cross-over trials; 11 participants not specified). Eighteen trials used a placebo
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