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Effectiveness of metformin for weight control in pediatric patients on SGA

二甲双胍对 SGA 儿童患者体重控制的有效性

基本信息

批准号：
10307598
负责人：
Hua Chen
金额：
$ 19.79万
依托单位：
UNIVERSITY OF HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10307598
关键词：
Adjuvant Adjuvant Study Adolescent Adult Adverse effects Affect Age Antidiabetic Drugs Antipsychotic Agents Appearance Body Image Body Weight decreased Body mass index Cardiovascular Diseases Child Childhood Clinical Computerized Medical Record Data Databases Dependence Development Early Intervention Effectiveness Emotional Generations Goals Individual Insulin Resistance Intervention Lead Literature Measures Mental disorders Metformin Modeling Non-Insulin-Dependent Diabetes Mellitus Obesity Onset of illness Overweight Patients Pharmaceutical Preparations Placebo Control Population Prevention Preventive Psychiatry Research Risk Safety Sample Size Sampling Testing Time TimeLine Translating Variant Vulnerable Populations Weight Weight Gain Weight maintenance regimen Work aged attenuation autism spectrum disorder base cohort compare effectiveness evidence base experience follow-up improved innovation medication compliance mental disorder diagnosis novel patient safety patient subsets pediatric patients preventive intervention self esteem sex side effect treatment adherence week trial weight gain prevention

项目摘要

PROJECT SUMMARY: Antipsychotic-induced Weight Gain (AIWG) affects up to 80% of children taking atypical/second generation antipsychotic (SGA) drugs. Changes in the physical appearance can lead to poor medication adherence. Childhood onset obesity carries a greater risk for type 2 diabetes and cardiovascular diseases than its onset in adults. Metformin is the most extensively studied adjuvant intervention for the management of AIWG in adults. In children and adolescents, the data are consistent but much more limited. The beneficial effect of adjuvant metformin established in trials has yet to be examined in real world SGA recipients. Our prior work found that most of the AIWG in children and adolescents happened during the first three months of SGA treatment, and SGA discontinuation only reversed a quarter of the weight patient gained during the treatment within one year of SGA cessation. The timeline for AIWG and its limited reversibility highlights the importance of AIWG prevention and early intervention, however, the optimal timing for adjuvant metformin initiation has not been investigated in the pediatric population. It is known that children and adolescents follow distinctively different weight development trajectories. Our preliminary findings suggest similar variations may also exist in pediatric AIWG. It remains unknown whether individuals following the different trajectories also respond differently to adjuvant metformin. The GOAL of the proposed study is to comprehensively examine the effectiveness of adjuvant metformin in a real world sample. To achieve the goal, we will identify children and adolescents aged 6 to 19 years who were treatment naive and received adjuvant metformin during the first 24 months of SGA treatment using a large national electronic medical record (EMR) database. The adjuvant metformin recipients are further categorized as early, intermediate and late initiators based on the period between SGA commencement and metformin initiation. The proposed study has two specific aims: Aim I: To compare the effectiveness of 1) adjuvant metformin on AIWG between propensity score weights matched 1) users and non- users, and among matched 2) early, intermediate, and late initiators using weighted linear mixed model with repeated measures. Aim II: To identify patient subgroups following certain weight development trajectories who are most likely to benefit from 1) the use adjuvant metformin, and from 2) the early initiation of metformin using group-based trajectory modeling integrated with propensity score. We hypothesize that H1: There is less increase in age-sex-specific weight z score when comparing 1) adjuvant metformin users vs. non-users, and when comparing 2) early and intermediate initiators vs. late initiators during a 12-month period since metformin initiation. H2: The magnitude of adjuvant metformin effect on AIWG, and the dependency of its effect upon the stage of SGA treatment at metformin initiation differ in patients following various weight trajectories. The proposed project will test new hypotheses using novel analytical approaches. The findings will provide new evidence to support the management of pediatric AIWG, and improve patient safety.

项目概要：抗精神病药物引起的体重增加（AIWG）影响多达80%服用非典型/第二代药物的儿童抗精神病药物（SGA）。身体外观的变化可能导致药物依从性差。儿童期肥胖比儿童期肥胖更容易患2型糖尿病和心血管疾病。成年人了二甲双胍是成人AIWG管理中研究最广泛的辅助干预措施。在儿童和青少年中，数据是一致的，但更为有限。佐剂的有益作用二甲双胍在临床试验中的应用还有待于在真实的世界SGA接受者中进行检验。我们之前的研究发现，大多数儿童和青少年AIWG发生在SGA治疗的前三个月，在一年内，SGA停药仅逆转了治疗期间患者体重增加的四分之一关于SGA停止AIWG的时间轴及其有限的可逆性突出了AIWG的重要性然而，辅助性二甲双胍启动的最佳时机尚未确定，在儿科人群中进行研究。众所周知，儿童和青少年遵循明显不同的体重发展轨迹我们的初步研究结果表明，类似的变化也可能存在于儿童 AIWG.目前尚不清楚遵循不同轨迹的个体是否也对不同的行为做出不同的反应。辅助二甲双胍。拟议研究的目的是全面研究辅助二甲双胍在真实的世界样本中。为了实现这一目标，我们将确定年龄在 6 - 19岁，未接受过治疗，在SGA的前24个月内接受二甲双胍辅助治疗使用大型国家电子病历（EMR）数据库进行治疗。二甲双胍辅助接受者根据SGA之间的时间，进一步分为早期、中期和晚期启动者开始和二甲双胍开始。这项研究有两个具体目标：目标一：比较 1）倾向评分权重匹配1）使用者和非使用者之间二甲双胍辅助治疗AIWG的有效性使用加权线性混合模型，在匹配的2）早期，中期和晚期启动者之间，反复的措施。目的II：确定遵循某些体重发展轨迹的患者亚组最有可能受益于1）使用二甲双胍辅助治疗和2）早期开始二甲双胍治疗的患者使用基于群体的轨迹建模与倾向评分相结合。我们假设H1：当比较1）二甲双胍辅助使用者与非使用者时，年龄-性别-特异性体重z评分增加，以及当比较2）二甲双胍给药后12个月内早期和中期启动与晚期启动时入会仪式H2：二甲双胍对AIWG的辅助作用的大小及其作用对不同体重轨迹患者开始二甲双胍时SGA治疗阶段不同。的拟议的项目将使用新的分析方法测试新的假设。研究结果将提供新的支持儿科AIWG管理的证据，并提高患者安全性。