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

• 批准号: 10428610
• 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
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428610
• 关键词: Adherence; Adjuvant; Admission activity; Adverse event; American; Antidiabetic Drugs; Benefits and Risks; Calibration; Cardiovascular system; Cesarean section; Characteristics; Clinical; Clinical Trials; Computerized Medical Record; Confidence Intervals; Congenital Abnormality; Data; Databases; Defect; Diabetes Mellitus; Diagnosis; Discipline of obstetrics; Dose; Drug Exposure; Dystocia; Ensure; Equilibrium; Exposure to; Fetal safety; First Pregnancy Trimester; General Population; Gestational Diabetes; 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; Neuraxis; 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; base; blood glucose regulation; clinical practice; cohort; college; comparative; comparative safety; comparison group; diabetes control; diabetic; diet and exercise; 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

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，非胰岛素药物已被广泛接受用于治疗2型糖尿病，