Comparative Safety of Non-Insulin Agents in Pregnant Women with Pregestational Diabetes

非胰岛素药物治疗妊娠期糖尿病孕妇的安全性比较

基本信息

批准号：
10620228
负责人：
Sonia Hernandez-Diaz
金额：
$ 56.22万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10620228
关键词：
Adherence Adjuvant Admission activity Adverse event American Antidiabetic Drugs Benefits and Risks Calibration Cardiovascular system Central Nervous System Cesarean section Characteristics Clinical Clinical Trials Computerized Medical Record Confidence Intervals Congenital Abnormality Data Databases Defect Diabetes Mellitus Diagnosis Diet Discipline of obstetrics Dose Drug Exposure Dystocia Ensure Equilibrium Exclusion Exercise Exposure to Fetal safety First Pregnancy Trimester General Population Glucose Glycosylated hemoglobin A Guidelines Gynecology Health Healthcare Hyperbilirubinemia Hypoglycemia Induced Labor Infant Injections Insulin Laboratories Late pregnancy Life Linear Models Link Medicaid Metformin Neonatal Hypoglycemia New Agents Non-Insulin-Dependent Diabetes Mellitus Observational Study Oral Organogenesis Outcome Outpatients Patients Pattern Pharmaceutical Preparations Pharmacy facility Planned Pregnancy Polyhydramnios Population Pre-Eclampsia Pregnancy Pregnancy Outcome Pregnancy in Diabetics Pregnant Women Premature Birth Procedures Randomized, Controlled Trials Recommendation Records Relative Risks Research Research Design Research Personnel Respiratory distress Risk Safety Sample Size Severities Shoulder Small for Gestational Age Infant Stratification Sulfonylurea Compounds Surveys Testing Therapeutic Time Time trend United States United States Food and Drug Administration Woman Work active comparator adverse outcome adverse pregnancy outcome blood glucose regulation clinical practice cohort college comparative comparative safety comparison group diabetes control diabetic early pregnancy evidence base fetal glycemic control health care service utilization improved innovation malformation maternal risk maternal safety medical complication neonatal outcome novel population based pregnant prenatal subcutaneous treatment guidelines treatment strategy unintended pregnancy

项目摘要

In the general population, non-insulin agents have gained wide acceptance for the treatment of type 2 diabetes, given their efficacy and tolerability when compared to subcutaneous insulin injections. One of the most common medical complications in pregnancy is pre-gestational diabetes and its management currently focuses on achieving glucose control with diet, exercise and, if needed, insulin treatment. Both the American Diabetes Association and the College of Obstetrics and Gynecology recommend to women planning pregnancy and for those who are pregnant that oral antidiabetic agents be substituted with insulin therapy until further data regarding safety become available. However, pregnant women are commonly exposed to these agents because 1) guidelines are not universally followed, 2) some women refuse to use insulin, and 3) 50% of pregnancies are unplanned and if a woman is already using an oral agent there is no time to switch to insulin before organogenesis. Furthermore, in pregnancy, oral agents have potential benefits with respect to patient acceptability and adherence, and therefore improved glycemic control and pregnancy outcomes. Even for those patients for whom oral antidiabetic agents alone are inadequate to achieve glycemic control, they can be used to reduce insulin dose. Since randomized controlled trials in pregnancy with sufficient sample size to define the safety of these agents robustly are not realistic, we need timely information based on carefully conducted observational studies. Until then, the lack of information will continue to be a critical barrier to their use in pregnancy. Our primary objective is to quantify the risk of maternal and fetal adverse events associated with specific non-insulin antidiabetic therapies during pregnancy in comparison to insulin alone and metformin alone. We have established a cohort of 3 million pregnancies linked to infants with longitudinal information on prescriptions and clinical conditions within two population-based healthcare databases: the Medicaid Analytic eXtract (MAX) and Truven Health MarketScan (Truven). This study will identify cohorts of over 18,000 (MAX) and 15,000 (Truven) women with pre-gestational type 2 diabetes who delivered in 2000-2018. Drug exposure will be determined based on pharmacy dispensing records, and outcomes will be based on in- and outpatient diagnoses and procedures, using validated definitions. To control for diabetes severity and other confounders, we will (i) restrict the population to women with type 2 diabetes; (ii) use an active reference group; (iii) use propensity score stratification to balance aspects of diabetes severity; and (iv) use a novel propensity score calibration approach to further adjust by incorporating data on glycemic control from subsamples with either laboratory records or linked electronic medical records. Data from nationally-representative surveys will be used to ensure generalizability to the US population. Generalized linear models will estimate relative risks and their 95% confidence intervals. Sensitivity analyses will be conducted to test the robustness of the findings. Prior work by the investigators and pilot data support the feasibility of the proposed study.

在一般人群中，非胰岛素药物治疗 2 型糖尿病已获得广泛接受，与皮下注射胰岛素相比，其功效和耐受性良好。最常见的一种妊娠期医学并发症是妊娠前糖尿病，目前其管理重点是通过饮食、运动以及胰岛素治疗（如果需要）实现血糖控制。美国糖尿病协会和妇产科学院向计划怀孕和怀孕的女性推荐孕妇应用胰岛素治疗替代口服降糖药，直至获得进一步数据关于安全性变得可用。然而，孕妇通常会接触这些物质，因为 1) 指南并未得到普遍遵循，2) 一些女性拒绝使用胰岛素，3) 50% 的怀孕是在计划外，如果女性已经在使用口服药物，则之前没有时间改用胰岛素器官发生。此外，在怀孕期间，口服药物对患者有潜在的好处可接受性和依从性，从而改善血糖控制和妊娠结局。即使对于那些对于单纯口服降糖药不足以控制血糖的患者，可以使用以减少胰岛素剂量。由于妊娠期随机对照试验有足够的样本量来定义这些药物的安全性稳健是不现实的，我们需要基于仔细进行的及时信息观察性研究。在那之前，信息的缺乏将继续成为其在实际应用中使用的一个关键障碍。怀孕。我们的主要目标是量化与以下因素相关的母婴不良事件的风险：与单独使用胰岛素和单独使用二甲双胍相比，妊娠期间特定的非胰岛素抗糖尿病治疗。我们建立了一个包含 300 万例与婴儿相关的妊娠的队列，并提供了以下方面的纵向信息：两个基于人群的医疗保健数据库中的处方和临床状况：医疗补助分析 eXtract (MAX) 和 Truven Health MarketScan (Truven)。这项研究将确定超过 18,000 人的队列（最多）以及 2000 年至 2018 年期间分娩的 15,000 名 (Truven) 患有孕前 2 型糖尿病的女性。药物暴露将根据药房配药记录确定，结果将根据住院和门诊患者情况而定使用经过验证的定义进行诊断和程序。为了控制糖尿病的严重程度和其他混杂因素，我们将 (i) 将人群限制为患有 2 型糖尿病的女性； (ii) 使用活跃的参考组； (三) 使用倾向评分分层以平衡糖尿病严重程度的各个方面； (iv) 使用新颖的倾向评分校准方法通过将子样本的血糖控制数据与任一实验室记录或链接的电子病历。将使用来自全国代表性调查的数据确保对美国民众的普遍适用性。广义线性模型将估计相对风险及其风险 95% 置信区间。将进行敏感性分析以测试研究结果的稳健性。之前的工作研究人员和试点数据支持了拟议研究的可行性。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Antidiabetic medication use during pregnancy: an international utilization study.

怀孕期间抗糖尿病药物的使用：一项国际利用研究。

DOI：
发表时间：
2019
期刊：
影响因子：
4.1
作者：
Cesta, Carolyn E;Cohen, Jacqueline M;Pazzagli, Laura;Bateman, Brian T;Bröms, Gabriella;Einarsdóttir, Kristjana;Furu, Kari;Havard, Alys;Heino, Anna;Hernandez;Huybrechts, Krista F;Karlstad, Øystein;Kieler, Helle;Li, Jiong;Leinonen
通讯作者：
Leinonen