Division of Research, Kaiser Permanente Northern California, Oakland.
Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California.
JAMA Netw Open. 2022 Mar 1;5(3):e225026. doi: 10.1001/jamanetworkopen.2022.5026.
Nearly 30% of individuals with gestational diabetes (GDM) do not achieve glycemic control with lifestyle modification alone and require medication treatment. Oral agents, such as glyburide, have several advantages over insulin for the treatment of GDM, including greater patient acceptance; however, the effectiveness of glyburide for the treatment of GDM remains controversial.
To compare the perinatal and neonatal outcomes associated with glyburide vs insulin using causal inference methods in a clinical setting with information on glycemic control.
DESIGN, SETTING, AND PARTICIPANTS: The population-based cohort study included patients with GDM who required medication treatment from 2007 to 2017 in Kaiser Permanente Northern California. Machine learning and rigorous casual inference methods with time-varying exposures were used to evaluate associations of exposure to glyburide vs insulin with perinatal outcomes. Data analysis was conducted from March 2018 to July 2017.
Time-varying exposure to glyburide vs insulin during pregnancy.
Outcomes evaluated separately included neonatal hypoglycemia, jaundice, shoulder dystocia, respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, size-for-gestational age, and cesarean delivery. Inverse probability weighting (IPW) estimation was used to separately compare perinatal outcomes between those initiating glyburide and insulin. This approach was combined with Super Learning for propensity score estimation to account for both baseline and time-dependent confounding in both per-protocol (primary) and intention-to-treat (secondary) analyses to evaluate sustained exposure to the same therapy.
From 2007 to 2017, 11 321 patients with GDM (mean [SD] age, 32.9 [4.9] years) initiated glyburide or insulin during pregnancy. In multivariate models, the risk of neonatal respiratory distress was 2.03 (95% CI, 0.13-3.92) per 100 births lower and the risk of NICU admission was 3.32 (95% CI, 0.20-6.45) per 100 births lower after continuous exposure to glyburide compared with insulin. There were no statistically significant differences in glyburide vs insulin initiation in risk for neonatal hypoglycemia (0.85 [95% CI, -1.17 to 2.86] per 100 births), jaundice (0.02 [95% CI, -1.46 to 1.51] per 100 births), shoulder dystocia (-1.05 [95% CI, -2.71 to 0.62] per 100 births), or large-for-gestational age categories (-2.75 [95% CI, -6.31 to 0.80] per 100 births).
Using data from a clinical setting and contemporary causal inference methods, our findings do not provide evidence of a difference in the outcomes examined between patients with GDM initiating glyburide compared with those initiating insulin.
近 30%的妊娠糖尿病 (GDM) 患者仅通过生活方式改变无法控制血糖，需要药物治疗。与胰岛素相比，口服药物如格列本脲在治疗 GDM 方面具有多项优势，包括患者接受度更高；然而，格列本脲治疗 GDM 的有效性仍存在争议。
在有血糖控制信息的临床环境中，使用因果推理方法比较格列本脲与胰岛素治疗与围产期和新生儿结局相关的情况。
设计、地点和参与者：这项基于人群的队列研究纳入了 2007 年至 2017 年期间在 Kaiser Permanente Northern California 需要药物治疗的 GDM 患者。使用机器学习和严格的时间变化暴露因果推理方法来评估暴露于格列本脲与胰岛素与围产期结局的关联。数据分析于 2018 年 3 月至 2017 年 7 月进行。
妊娠期间格列本脲与胰岛素的时间变化暴露情况。
分别评估的结局包括新生儿低血糖、黄疸、肩难产、呼吸窘迫综合征 (RDS)、新生儿重症监护病房 (NICU) 入院、胎儿大小与胎龄比例和剖宫产。采用逆概率加权（Inverse Probability Weighting，IPW）估计分别比较开始使用格列本脲和胰岛素的患者的围产期结局。该方法与超级学习（Super Learning）相结合，用于倾向评分估计，以同时考虑基线和时间依赖性混杂因素，包括方案内（主要）和意向治疗（次要）分析中的持续性暴露于相同治疗方法，以评估持续暴露于相同治疗方法的效果。
2007 年至 2017 年间，11321 名患有 GDM 的患者（平均[标准差]年龄，32.9[4.9]岁）在妊娠期间开始使用格列本脲或胰岛素。在多变量模型中，与胰岛素相比，连续暴露于格列本脲可使新生儿呼吸窘迫的风险降低 2.03（95%CI，0.13-3.92）/每 100 例出生，NICU 入院的风险降低 3.32（95%CI，0.20-6.45）/每 100 例出生。与胰岛素相比，开始使用格列本脲在新生儿低血糖（每 100 例出生 0.85[95%CI，-1.17 至 2.86]）、黄疸（每 100 例出生 0.02[95%CI，-1.46 至 1.51]）、肩难产（每 100 例出生-1.05[95%CI，-2.71 至 0.62]）或大于胎龄儿（每 100 例出生-2.75[95%CI，-6.31 至 0.80]）的风险方面没有统计学上的显著差异。
使用来自临床环境的数据和当代因果推理方法，我们的研究结果并未提供证据表明 GDM 患者开始使用格列本脲与开始使用胰岛素相比，检查结果存在差异。
