Effectiveness of metformin for weight control in pediatric patients on SGA

项目总结： 抗精神病药物引起的体重增加(AIWG)影响高达80%服用非典型/第二代药物的儿童 抗精神病(SGA)药物。身体外观的变化可能会导致服药依从性差。 儿童起病的肥胖症患2型糖尿病和心血管疾病的风险比起病的儿童高. 成年人。二甲双胍是成人AIWG治疗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，但要有限得多。佐剂的有益作用 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。我们之前的工作发现 大多数儿童和青少年的AIWG发生在SGA治疗的前三个月，并且 停用SGA仅能在一年内逆转患者在治疗过程中增加的四分之一的体重 停止使用SGA。AIWG的时间表及其有限的可逆性突出了AIWG的重要性 预防和早期干预，然而，佐剂二甲双胍的最佳启动时机尚未确定 在儿科人群中进行了调查。众所周知，儿童和青少年遵循的规则截然不同。 体重发展轨迹。我们的初步发现表明，类似的变异也可能存在于儿科 AIWG。目前尚不清楚遵循不同轨迹的个体是否也会对 佐剂二甲双胍。拟议研究的目标是全面审查 真实世界样本中的佐剂二甲双胍。为了实现这一目标，我们将识别年龄为 6至19岁未接受治疗并在SGA的前24个月接受佐剂二甲双胍治疗的患者 使用大型国家电子病历(EMR)数据库进行治疗。二甲双胍佐剂受体 根据SGA之间的时间间隔，进一步将其分为早期、中期和晚期发起者 开始和二甲双胍启动剂。拟议的研究有两个具体目标：目标一：比较 1)佐剂二甲双胍对1)使用者与非使用者的AIWG的影响 用户，以及2)匹配的早期、中期和晚期发起者之间使用加权线性混合模型 反复采取措施。目标II：确定遵循特定体重发展轨迹的患者亚组 谁最有可能受益于1)使用佐剂二甲双胍，以及2)早期开始使用二甲双胍 采用基于群体的轨迹建模，结合倾向性评分。我们假设H1：有更少的 在比较1)二甲双胍佐剂使用者与非使用者时，年龄-性别特定体重z分数的增加，以及 比较2)自二甲双胍以来12个月内早期和中期发起者与晚期发起者 入会仪式。H2：二甲双胍对AIWG的佐剂作用的大小，以及其作用依赖于 在遵循不同体重轨迹的患者中，二甲双胍开始时的SGA治疗阶段不同。这个 拟议的项目将使用新的分析方法来检验新的假设。这些发现将为我们提供新的 支持儿科AIWG管理，提高患者安全性的证据。

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.