PDF(Pubmed)
Abstract：
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective medications for the treatment of type 2 diabetes and obesity. Pharmacological studies in rodents support an association between the use of GLP-1 RAs and the development of medullary thyroid cancer (MTC) resulting in a black box warning for these agents in patients at risk for this condition. Yet, the association between GLP-1 RAs and non-MTC remains controversial. Excessive worry about unproven thyroid cancer risk might lead to underutilizing GLP-1 RAs in patients who could otherwise experience substantial benefits. Unwarranted concerns about thyroid cancer could lead to unnecessary thyroid cancer screening and harms from overdiagnosis. Summary: The body of evidence assessing the association between GLP-1 RA use and thyroid cancer spans a wide range of methodologies, including basic and translational research investigating biological plausibility; randomized trials assessing clinical efficacy and providing the strongest evidence for causality; observational studies providing real-life outcome evaluation in larger populations but with limited evaluation of covariates or dependable outcome definitions; and pharmacovigilance studies that provide postmarketing assessments of a safety signal but do not address causality. There is biological plausibility supporting an association between GLP-1 RA and MTC in rodents, which is less clear for non-MTC in humans. Clinical evidence from randomized trials and associated meta-analysis suggest thyroid cancer as a rare event making effect estimates imprecise but without conclusive and consistent evidence of increase risk in those receiving GLP-1 RA. Observational studies at higher risk of bias also show low event rates for thyroid cancer, with effect estimates that are inconsistent among different studies. Pharmacovigilance studies consistently show a signal of increased reporting of thyroid cancer in patients treated with GLP-1 RA. Conclusions: Evidence from randomized controlled trials indicates occurrence of thyroid cancer is infrequent in individuals exposed to GLP-1 RA. Observational studies at higher risk of bias yield inconsistent results. Overall there is no conclusive evidence of elevated thyroid cancer risk. These findings can help clinicians when addressing patient\'s concerns about a potential yet unproven link between GLP-1 RA therapy and thyroid cancer.
摘要：
背景：GLP-1受体激动剂是治疗2型糖尿病和肥胖症的高效药物。啮齿动物的药理学研究支持GLP-1受体激动剂的使用与甲状腺髓样癌的发展之间的关联，导致在有这种情况风险的患者中这些药物的黑匣子警告。然而，GLP-1受体激动剂与非甲状腺髓样癌之间的关联仍存在争议.过度担心未经证实的甲状腺癌风险可能会导致GLP-1受体激动剂在患者中使用不足，否则他们可能会获得实质性益处。对甲状腺癌的不必要的担忧可能导致不必要的甲状腺癌筛查和过度诊断的危害。
结论：评估GLP-1RA使用与甲状腺癌之间关联的大量证据涵盖了多种方法，包括研究生物学合理性的基础和转化研究;评估临床疗效并提供最有力因果关系证据的随机试验;在较大人群中提供真实结局评估的观察性研究,但对协变量或可靠结局定义的评估有限;以及提供安全性信号上市后评估但不解决因果关系的药物警戒性研究。有生物学上的合理性支持GLP-1RA和啮齿动物甲状腺髓样癌之间的关联，这对于人类的非甲状腺髓样癌来说不太清楚。来自随机试验和相关荟萃分析的临床证据表明，甲状腺癌是一种罕见事件，因此效果估计不准确，但没有结论性和一致的证据表明接受GLP-1RA的患者风险增加。偏倚风险较高的观察性研究，甲状腺癌的事件发生率也很低，效果估计在不同的研究中不一致。药物警戒研究一致显示，在接受GLP-1RA治疗的患者中，甲状腺癌的报告增加。
结论：来自随机对照试验的证据表明，暴露于GLP-1RA的个体很少发生甲状腺癌。偏倚风险较高的观察性研究结果不一致。总体而言，没有确凿的证据表明甲状腺癌风险升高。这些发现可以帮助临床医生解决患者对GLP-1RA治疗与甲状腺癌之间潜在但未经证实的联系的担忧。.
结论：评估GLP-1RA使用与甲状腺癌之间关联的大量证据涵盖了多种方法，包括研究生物学合理性的基础和转化研究;评估临床疗效并提供最有力因果关系证据的随机试验;在较大人群中提供真实结局评估的观察性研究,但对协变量或可靠结局定义的评估有限;以及提供安全性信号上市后评估但不解决因果关系的药物警戒性研究。有生物学上的合理性支持GLP-1RA和啮齿动物甲状腺髓样癌之间的关联，这对于人类的非甲状腺髓样癌来说不太清楚。来自随机试验和相关荟萃分析的临床证据表明，甲状腺癌是一种罕见事件，因此效果估计不准确，但没有结论性和一致的证据表明接受GLP-1RA的患者风险增加。偏倚风险较高的观察性研究，甲状腺癌的事件发生率也很低，效果估计在不同的研究中不一致。药物警戒研究一致显示，在接受GLP-1RA治疗的患者中，甲状腺癌的报告增加。
结论：来自随机对照试验的证据表明，暴露于GLP-1RA的个体很少发生甲状腺癌。偏倚风险较高的观察性研究结果不一致。总体而言，没有确凿的证据表明甲状腺癌风险升高。这些发现可以帮助临床医生解决患者对GLP-1RA治疗与甲状腺癌之间潜在但未经证实的联系的担忧。.
