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.

项目摘要：抗精神病药引起的体重增加（AIWG）最多影响80％的服用非典型/第二代儿童抗精神病药（SGA）药物。外观的变化会导致药物依从性不佳。儿童时期肥胖具有比其发作的2型糖尿病和心血管疾病更大的风险成年人。二甲双胍是成人管理AIWG的最广泛研究的辅助干预措施。在儿童和青少年中，数据是一致的，但更有限。佐剂的有益效果在试验中建立的二甲双胍尚未在现实世界的SGA接受者中进行检查。我们先前的工作发现儿童和青少年的大多数AIWG发生在SGA治疗的前三个月中， SGA停用仅逆转了一年内在治疗期间获得的体重患者的四分之一 SGA戒烟。 AIWG的时间表及其有限的可逆性突出了AIWG的重要性但是，预防和早期干预，辅助二甲双胍启动的最佳时机尚未在儿科人群中进行了调查。众所周知，儿童和青少年遵循明显不同的体重发育轨迹。我们的初步发现表明小儿可能也存在类似的变化 aiwg。遵循不同轨迹的个人是否对辅助二甲双胍。拟议的研究的目的是全面研究现实世界样本中的辅助二甲双胍。为了实现目标，我们将确定年龄的儿童和青少年在SGA的前24个月内，有6至19岁的治疗幼稚并接受了辅助二甲双胍使用大型国家电子病历（EMR）数据库进行处理。辅助二甲双胍接受者根据SGA之间的期间，进一步归类为早期，中级和晚期启动器开始和二甲双胍的启动。拟议的研究有两个具体的目的：目标I：比较 1）辅助二甲双胍对AIWG的辅助分数匹配1）用户和非 - 用户以及匹配的2）早期，中间和晚期发起人使用加权线性混合模型与重复措施。 AIM II：确定一定体重发育轨迹的患者子组谁最有可能从1）使用辅助二甲双胍，以及2）二甲双胍的早期开始使用基于组的轨迹建模与倾向得分集成。我们假设H1：少比较时，年龄性别特定的体重z评分增加1）辅助二甲双胍用户与非用户的分数和比较2）自二甲双胍以来的12个月内，早期和中级发起人与晚期发起人引发。 H2：佐剂二甲双胍对AIWG的影响及其对aiwg的依赖性在各种体重轨迹的患者中，二甲双胍启动时的SGA治疗阶段不同。这拟议的项目将使用新颖的分析方法检验新的假设。这些发现将提供新的支持小儿AIWG管理并提高患者安全的证据。