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探讨:基于证据的系统回顾

    Safety of Continued Pregnancy Following Exposure to Glucagon-like Peptide-1 Receptor Agonists During Gestation: An Evidence-Based Systematic Review

    • 摘要:
      目的 探讨胰高血糖素样肽-1受体激动剂(glucagon-like peptide-1 receptor agonist,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,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 glucagon-like peptide-1 receptor agonist(GLP-1RA) 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 systematically searched 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 Review Manager 5.4 software.
      RESULTS A total of 14 studies were included, comprising 3 cohort studies and 11 case series/case report studies. The results of the meta-analysis of the 3 cohort studies showed that, compared with pregnant women not exposed to GLP-1RA, exposure to GLP-1RA 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 might 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-1RA, 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 while exposure to GLP-1RA during pregnancy may reduce live birth rate, it does not increase incidence of major congenital malformations, preterm birth, or small-for-gestational-age newborns. Disease and different GLP-1RA may be confounding factors, and further high-quality data are needed for validation.

       

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