The only pharmacologic treatment for gestational diabetes (GDM) approved by U.S. Food and Drug Administration is insulin. However, due to improved ease of use and lower cost, oral antidiabetic medications, such as glyburide, are prescribed more commonly than insulin. We investigate glyburide's impact on two adverse perinatal outcomes compared to medical nutritional therapy, the universal first-line therapy, in a large, population-based cohort. At the design stage, we employ matching to select comparable treated subjects(received glyburide) and controls (received medical nutritional therapy). Multiple background variables were associated with GDM treatment modality and perinatal outcomes; however, there is ambiguity about which of the many potential confounding variables should be prioritized in matching. Standard selection methods based on treatment imbalance alone neglect variables' relationships with the outcome. Thus, we propose the joint variable importance plot (jointVIP) to guide variable prioritization for this study. This plot adds outcome associations on a second dimension to better contextualize standard imbalance measures, further enhances variable comparisons using unadjusted bias curves derived under the omitted variable bias framework, and can produce recommended values for tuning parameters in existing methods. After forming matched pairs, we conduct inference for adverse effects of glyburide and perform sensitivity analyses to assess the potential role of unmeasured confounding. Our findings of no reliable adverse effect of glyburide inform future pharmacologic treatment strategies to manage GDM.

翻译：美国食品药品监督管理局批准的妊娠期糖尿病（GDM）唯一药物治疗方案为胰岛素。然而，由于使用便捷性和成本较低，格列本脲等口服抗糖尿病药物的处方量已超过胰岛素。本研究在大型人群队列中，探究与通用一线治疗（医学营养治疗）相比，格列本脲对两种不良围产期结局的影响。在设计阶段，我们采用匹配方法选择具有可比性的治疗组（接受格列本脲）与对照组（接受医学营养治疗）。多种背景变量与GDM治疗方式及围产期结局相关，但关于匹配中应优先考虑哪些潜在混杂变量仍存在模糊性。基于单一治疗失衡的标准选择方法忽略了变量与结局的关联。因此，我们提出联合变量重要性图以指导本研究中的变量优先排序。该图在第二维度增加结局关联性以更好阐释标准失衡测量指标，利用遗漏变量偏倚框架下推导的未调整偏倚曲线强化变量比较，并可针对现有方法中的调优参数生成推荐值。完成匹配后，我们对格列本脲的不良效应进行推断，并通过敏感性分析评估未测量混杂因素的潜在影响。本研究发现格列本脲无可靠不良效应，为未来管理GDM的药理学治疗策略提供依据。