Effectiveness of pharmacological interventions for managing obesity in children and adolescents: A systematic review and meta-analysis framed using minimal important difference estimates based on GRADE guidance to inform a clinical practice guideline

IF 2.7 3区医学 Q1 PEDIATRICS

Pediatric Obesity Pub Date : 2024-09-06 DOI:10.1111/ijpo.13169

Gita Wahi, Julie St-Pierre, Bradley C. Johnston, Donna Fitzpatrick-Lewis, Ali Usman, Diana Sherifali, Roah Merdad, Zahra Esmaeilinezhad, Catherine S. Birken, Jill Hamilton, Mélanie Henderson, Sarah A. Moore, Geoff D. C. Ball, Katherine M. Morrison, the Steering Committee for Updating Canada's Clinical Practice Guideline for Managing Pediatric Obesity

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Abstract

Objective

To summarize the literature on pharmacotherapy for managing paediatric obesity.

Methods

A systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) with <18-year-olds of pharmacotherapeutic agents published up to November 2022. Estimates of effect for outcomes were presented relative to minimal important differences and GRADE certainty of evidence. We examined data on patient/proxy-reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry and adverse events (AEs).

Results

Overall, 35 RCTs were included. Trials examined metformin (n = 26), glucagon-like peptide-1 receptor agonists (GLP1RAs) (n = 7) and a lipase inhibitor (orlistat; n = 2). Intervention duration varied (3−24 months). Metformin had little to no benefit on PROMs (e.g., health-related quality of life [HRQoL]; 6 RCTs), moderate reductions in triglycerides, a moderate decline in insulin resistance, a small to moderate decline in BMI z-score (BMIz) and a moderate increase in mild to moderate gastrointestinal AEs. Response to GLP1RAs was heterogeneous and results of subgroup analysis demonstrated variability of impact. Liraglutide (2 RCTs) resulted in a small reduction in HOMA-IR and BMIz, but little to no benefit on other outcomes. Exenatide (4 RCTs) had a moderate reduction on blood pressure and a small decrease in BMIz with little to no benefit on other outcomes. Semaglutide (1 RCT) had a small benefit on HRQoL, a small reduction on SBP, a moderate reduction on total cholesterol and LDL-cholesterol, a large reduction on triglyceride, and a very large decline in BMIz accompanied by a small increase in mild to moderate gastrointestinal AEs. Orlistat had a moderate reduction in DBP and little to no benefit in other outcomes measured, but had a very large increased risk of mild to moderate gastrointestinal AEs. Serious AEs were rare and for interventions with sufficent AE reporting, were considered not likely attributable to the interventions.

Conclusion

Few studies examined the impact of pharmacotherapy on PROMs. There is evidence that metformin and GLP1RAs lead to important improvements in cardiometabolic and anthropometric outcomes while accompanied by mild to moderate AEs. Long-term effectiveness and safety of GLP1RAs remain to be evaluated.

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药物干预对控制儿童和青少年肥胖症的效果：根据 GRADE 指南，利用最小重要差异估计值进行系统回顾和荟萃分析，为临床实践指南提供信息。

目的总结有关控制儿童肥胖症的药物疗法的文献：结果：共纳入了 35 项随机对照试验：共纳入 35 项随机对照试验。试验研究了二甲双胍（26 例）、胰高血糖素样肽-1 受体激动剂（GLP1RAs）（7 例）和脂肪酶抑制剂（奥利司他；2 例）。干预时间长短不一（3-24 个月）。二甲双胍对PROMs（如健康相关生活质量[HRQoL]；6项RCTs）几乎没有益处，甘油三酯适度下降，胰岛素抵抗适度下降，体重指数z-score（BMIz）小幅至中度下降，轻度至中度胃肠道AEs适度增加。对 GLP1RAs 的反应不尽相同，亚组分析结果显示了影响的差异性。利拉鲁肽（2 项研究）导致 HOMA-IR 和 BMIz 略有下降，但对其他结果几乎没有益处。艾塞那肽（4 项研究）使血压适度降低，BMIz 略有下降，但对其他结果几乎没有益处。塞马鲁肽（1 项研究）对 HRQoL 有小幅改善，SBP 有小幅降低，总胆固醇和低密度脂蛋白胆固醇有中幅降低，甘油三酯有大幅降低，BMIz 有大幅下降，但轻度至中度胃肠道 AEs 有小幅增加。奥利司他可适度降低DBP，对其他测量结果几乎没有益处，但轻度至中度胃肠道不良反应的风险却大大增加。严重的AEs很少见，对于AE报告充分的干预措施，被认为不太可能归因于干预措施：很少有研究探讨药物治疗对 PROMs 的影响。有证据表明，二甲双胍和 GLP1RAs 可显著改善心脏代谢和人体测量结果，同时伴有轻度至中度 AE。GLP1RAs 的长期有效性和安全性仍有待评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric Obesity PEDIATRICS-

CiteScore

7.30

自引率

5.30%

发文量

117

审稿时长

6-12 weeks

期刊介绍： Pediatric Obesity is a peer-reviewed, monthly journal devoted to research into obesity during childhood and adolescence. The topic is currently at the centre of intense interest in the scientific community, and is of increasing concern to health policy-makers and the public at large. Pediatric Obesity has established itself as the leading journal for high quality papers in this field, including, but not limited to, the following: Genetic, molecular, biochemical and physiological aspects of obesity – basic, applied and clinical studies relating to mechanisms of the development of obesity throughout the life course and the consequent effects of obesity on health outcomes Metabolic consequences of child and adolescent obesity Epidemiological and population-based studies of child and adolescent overweight and obesity Measurement and diagnostic issues in assessing child and adolescent adiposity, physical activity and nutrition Clinical management of children and adolescents with obesity including studies of treatment and prevention Co-morbidities linked to child and adolescent obesity – mechanisms, assessment, and treatment Life-cycle factors eg familial, intrauterine and developmental aspects of child and adolescent obesity Nutrition security and the "double burden" of obesity and malnutrition Health promotion strategies around the issues of obesity, nutrition and physical activity in children and adolescents Community and public health measures to prevent overweight and obesity in children and adolescents.