Hedrington Maka S, Davis Stephen N
a Department of Medicine , University of Maryland School of Medicine , Baltimore , MD , USA.
Expert Opin Drug Metab Toxicol. 2017 Oct;13(10):1029-1038. doi: 10.1080/17425255.2017.1372423. Epub 2017 Sep 5.
Normal pregnancy development involves gradual decline in insulin sensitivity, which sometimes requires pharmacotherapy. Insulin is the drug of choice for gestational and pregestational diabetes. Metabolism of traditional insulins results in inadequate onset and duration of action and marked peak activity. These properties increase risk of excessive glucose excursions, which are especially undesirable during pregnancy. Insulin analogs have been emerging as a safer and more effective treatment of diabetes during pregnancy. Areas covered: This manuscript reviews currently used antihyperglycemic agents: fast and long-acting insulins, metformin and glyburide. Trials demonstrating their efficacy and safety during pregnancy are described. Certain drug metabolism considerations (e.g. affinity to IGF-1) are emphasized. Expert opinion: The theories that insulin analogs bind to immunoglobulin and cross placenta have been disproved. Lispro, aspart, glargine and detemir do not transfer across the placenta and do not result in adverse maternal and neonatal outcomes. In addition, favorable pharmacokinetic profiles (rapid onset and 24-hour near peakless activity) substantially reduce blood glucose variability including hypoglycemia. We believe that insulin analogs should be given strong consideration for the treatment of diabetes during pregnancy. Metformin has also proven to be safe and may be considered as an initial single agent for milder gestational diabetes.
正常妊娠发展过程中胰岛素敏感性会逐渐下降，有时需要药物治疗。胰岛素是妊娠期和孕前糖尿病的首选药物。传统胰岛素的代谢导致起效时间和作用持续时间不足，且活性峰值明显。这些特性增加了血糖过度波动的风险，而这在孕期尤其不可取。胰岛素类似物已逐渐成为孕期糖尿病更安全、更有效的治疗方法。涵盖领域：本文综述了目前使用的降糖药物：速效和长效胰岛素、二甲双胍和格列本脲。描述了证明它们在孕期有效性和安全性的试验。强调了某些药物代谢方面的考虑因素（如对胰岛素样生长因子-1的亲和力）。专家观点：胰岛素类似物与免疫球蛋白结合并穿过胎盘的理论已被否定。赖脯胰岛素、门冬胰岛素、甘精胰岛素和地特胰岛素不会穿过胎盘，也不会导致不良的母婴结局。此外，良好的药代动力学特性（起效迅速且24小时几乎无峰值活性）可大幅降低血糖变异性，包括低血糖。我们认为，胰岛素类似物应被优先考虑用于孕期糖尿病的治疗。二甲双胍也已被证明是安全的，可被视为轻度妊娠期糖尿病的初始单一用药。
