Drummond Rosa F, Seif Karl E, Reece E Albert
Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine and Medical Center, Baltimore, MD.
Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine and Medical Center, Baltimore, MD.
Am J Obstet Gynecol. 2025 Jan;232(1):17-25. doi: 10.1016/j.ajog.2024.08.024. Epub 2024 Aug 23.
Glucagon-like peptide-1 receptor agonists are peptide analogues that are used to treat type 2 diabetes mellitus and obesity. The first medication in this class, exenatide, was approved in 2005, and these medications, specifically semaglutide, have become more popular in recent years due to their pronounced effects on glycemic control, weight reduction, and cardiovascular health. Due to successful weight loss from these medications, many women previously diagnosed with oligomenorrhea and unable to conceive have experienced unplanned pregnancies while taking the medications. However, there are currently little data for clinicians to use in counseling patients in cases of accidental periconceptional exposure. In some studies examining small animals exposed to glucagon-like peptide-1 receptor agonists in pregnancy, there has been evidence of adverse outcomes in the offspring, including decreased fetal growth, skeletal and visceral anomalies, and embryonic death. Although there are no prospective studies in humans, case reports, cohort studies, and population-based studies have not shown a pattern of congenital anomalies in infants. A recent large, observational, population-based cohort study examined 938 pregnancies affected by type 2 diabetes mellitus and compared outcomes from periconceptional exposure to glucagon-like peptide-1 receptor agonists and insulin. The authors concluded there was not a significantly increased risk of major congenital malformations in patients taking glucagon-like peptide-1 receptor agonists, although there was no information on maternal glycemic control or diabetic fetopathy. As diabetic embryopathy is directly related to the degree of maternal hyperglycemia and not the diagnosis of diabetes itself, it is not possible to make this conclusion without this information. Furthermore, there is little evidence available regarding fetal growth restriction, embryonic or fetal death, or other potential complications. At this time, patients should be counseled there is not enough evidence to predict any adverse effects, or the lack thereof, of periconceptional exposure of glucagon-like peptide-1 receptor agonists during pregnancy. We recommend that all patients use contraception to prevent unintended pregnancy while taking glucagon-like peptide-1 receptor agonists.
胰高血糖素样肽-1受体激动剂是用于治疗2型糖尿病和肥胖症的肽类似物。该类中的第一种药物艾塞那肽于2005年获批，近年来，这些药物，尤其是司美格鲁肽，因其对血糖控制、体重减轻和心血管健康的显著作用而变得更受欢迎。由于这些药物成功减重，许多先前被诊断为月经过少且无法受孕的女性在服用这些药物期间意外怀孕。然而，目前临床医生在咨询意外孕期暴露患者时几乎没有可用数据。在一些研究中，对孕期接触胰高血糖素样肽-1受体激动剂的小动物进行了检查，有证据表明后代出现了不良后果，包括胎儿生长受限、骨骼和内脏异常以及胚胎死亡。虽然没有针对人类的前瞻性研究，但病例报告、队列研究和基于人群的研究均未显示婴儿存在先天性异常模式。最近一项大型的、基于人群的观察性队列研究对938例受2型糖尿病影响的妊娠进行了检查，并比较了孕期接触胰高血糖素样肽-1受体激动剂和胰岛素的结果。作者得出结论，服用胰高血糖素样肽-1受体激动剂的患者发生重大先天性畸形的风险没有显著增加，尽管没有关于母体血糖控制或糖尿病胎儿病变的信息。由于糖尿病胚胎病与母体高血糖程度直接相关，而非糖尿病本身的诊断，没有这些信息就无法得出这一结论。此外，关于胎儿生长受限、胚胎或胎儿死亡或其他潜在并发症的证据很少。目前，应告知患者，没有足够的证据来预测孕期接触胰高血糖素样肽-1受体激动剂的任何不良影响或缺乏不良影响。我们建议所有患者在服用胰高血糖素样肽-1受体激动剂期间采取避孕措施，以防止意外怀孕。
