妊娠期胰高血糖素样肽-1受体激动剂暴露后继续妊娠的安全性

Safety of Continuation of Pregnancy After Exposure to GLP-1 Receptor Agonists

关键词:  妊娠期  GLP-1RA  安全性  Meta分析  队列研究  病例系列/报告

Key words:  Pregnancy  GLP-1RA  Safety  Meta-analysis  Cohort study  Case series/report

摘要:

目的 探讨GLP-1RA用于妊娠期患者的安全性,为患者药学服务和临床治疗提供循证支持。方法 系统检索PubMed、Embase、The Cochrane Library、中国知网、万方数据库,搜集有关妊娠期妇女暴露GLP-1RA的临床研究,检索时间均为从建库起至2025年6月9日。由2位评价员独立筛选文献、提取资料并评价纳入研究的风险偏倚后,采用Review Manager 5.4软件进行Meta分析。结果 共纳入14项研究,包括3项队列研究、11项病例系列/报告研究。3项队列研究进行Meta分析结果显示,与妊娠期未暴露于GLP-1RA的妇女相比,妊娠期暴露于GLP-1RA未增加新生儿主要先天性畸形[RR=0.99,95%CI (0.79,1.24),P=0.90]、早产[RR=0.63,95% CI(0.41,0.97),P=0.03]、小于胎龄儿[RR=0.68,95% CI(0.39,1.19),P=0.18]发生率,但可能降低活产率[RR=0.90,95%CI (0.83,0.97),P=0.008]。11项病例系列/报告结果显示,24次妊娠暴露于GLP-1RA,其中15例次暴露于司美格鲁肽,3例次暴露于度拉糖肽,3例次暴露于利拉鲁肽,3例次妊娠暴露于艾塞那肽,仅1名胎儿出现严重心脏异常,1名男婴轻度双侧肾盂扩张外,其余22名均为健康新生儿。结论 当前有限证据表明,妊娠期暴露于GLP-1RA可能会降低活产率,但未增加新生儿主要先天性畸形、早产、小于胎龄儿发生率。疾病和不同GLP-1RA可能是混杂因素,尚需更多高质量数据验证。

Abstract:

OBJECTIVE To investigate the safety of GLP-1 receptor agonists (GLP-1RAs) in pregnant patients and provide evidence-based support for pharmaceutical services and clinical treatment for patients. METHODS?PubMed, Embase, The Cochrane Library, CNKI and Wanfang Database were systematic searches to collect studies of GLP-1RA) exposure? in pregnant women?from inception to June 9, 2025. Two reviewers independently screened literature, extracted data, and assessed the risk of bias in included studies. Meta-analysis was then performed by using RevMan 5.4 software. RESULTS?A total of 14 studies were included, comprising 3 cohort studies and 11 case series/case report studies. The results meta-analysis of the 3 cohort studies showed that, compared with pregnant women not exposed to GLP-1RAs, exposure to GLP-1RAs during pregnancy did not increase the risk of major congenital malformations in newborns (RR=0.99,95%CI 0.79 to 1.24, P=0.90), preterm birth (RR=0.63,95%CI 0.41 to 0.97 P=0.03) , or small for gestational age (RR=0.68,95%CI 0.39 to 1.19 P=0.18). However, it may reduce the live birth rate(RR=0.90,95%CI 0.83 to 0.97 P=0.008). Results from 11 case series/reports showed that 24 pregnancies were exposed to GLP-1RAs, including 15 exposures to semaglutide, 3 exposures to dulaglutide, and 3 exposures to liraglutide, and 3 pregnancies exposed to exenatide. Among these, only 1 fetus had severe cardiac abnormalities, and 1 male infant exhibited mild bilateral renal pyelectasis, while the remaining 22 were healthy newborns.CONCLUSION?Current limited evidence suggests that exposure to GLP-1RAs during pregnancy may reduce live birth rates but does not increase risks of major congenital malformations, preterm birth, or small for gestational age. Disease and different GLP-1RAs may be confounding factors, and further high-quality data are needed for validation.