Objective To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer. Design Scandinavian cohort study. Setting Denmark, Norway, and Sweden, 2007-21. Participants Patients who started GLP1 receptor agonist treatment were compared with patients who started dipeptidyl peptidase 4 (DPP4) inhibitor treatment, and in an additional analysis, patients who started sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. Main outcome measures Thyroid cancer identified from nationwide cancer registers. An active-comparator new user study design was used to minimise risks of confounding and time related biases from using real world studies of drug effects. Cox regression was used to estimate hazard ratios, controlling for potential confounders with propensity score weighting. Results The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per 10 000 person years) treated with GLP1 receptor agonists and 184 of 291 667 patients (incidence rate 1.46 events per 10 000 person years) treated with DPP4 inhibitors developed thyroid cancer. GLP1 receptor agonist use was not associated with increased risk of thyroid cancer (hazard ratio 0.93, 95% confidence interval 0.66 to 1.31; rate difference −0.13, 95% confidence interval −0.61 to 0.36 events per 10 000 person years). The hazard ratio for medullary thyroid cancer was 1.19 (0.37 to 3.86). In the additional analysis comparing the GLP1 receptor agonist group with the SGLT2 inhibitor group, the hazard ratio for thyroid cancer was 1.16 (0.65 to 2.05). Conclusions In this large cohort study using nationwide data from three countries, GLP1 receptor agonist use was not associated with a substantially increased risk of thyroid cancer over a mean follow-up of 3.9 years. In the main analysis comparing GLP1 receptor agonists with DPP4 inhibitors, the upper limit of the confidence interval was consistent with no more than a 31% increase in relative risk. No additional data available. The data analysed in this study were based on Scandinavian nationwide register. Individual level data from the registers can only be accessed through secure servers and only export of aggregated data, as presented in research articles, is allowed. Permission to access data can be made only after fulfilling specific requirements to safeguard the anonymity of the study participants and other data safety issues. For these reasons, data cannot be made generally available.

中文翻译：

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胰高血糖素样肽 1 受体激动剂的使用和甲状腺癌的风险：斯堪的纳维亚队列研究

目的 探讨使用胰高血糖素样肽 1 (GLP1) 受体激动剂是否与甲状腺癌风险增加相关。设计斯堪的纳维亚队列研究。设置丹麦、挪威和瑞典，2007-21。参与者将开始 GLP1 受体激动剂治疗的患者与开始二肽基肽酶 4 (DPP4) 抑制剂治疗的患者进行比较，并在另一项分析中，对开始钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂治疗的患者进行比较。主要结果指标 从全国癌症登记册中发现的甲状腺癌。采用主动比较器新用户研究设计来最大程度地减少使用真实世界药物作用研究带来的混杂和时间相关偏差的风险。 Cox 回归用于估计风险比，通过倾向评分加权控制潜在的混杂因素。结果 GLP1 受体激动剂组的平均随访时间为 3.9 年（标准差 3.5 年），DPP4 抑制剂组的平均随访时间为 5.4 年（标准差 3.5 年）。在接受 GLP1 受体激动剂治疗的 145 410 名患者中，有 76 名患者（发病率为每 10 000 人年 1.33 起事件），在接受 DPP4 抑制剂治疗的 291 667 名患者中（发病率为每 10 000 人年 1.46 起事件），有 184 名患者罹患甲状腺癌。 GLP1受体激动剂的使用与甲状腺癌风险增加无关（风险比0.93，95%置信区间0.66至1.31；率差-0.13，95%置信区间-0.61至0.36事件每10000人年）。甲状腺髓样癌的风险比为 1.19（0.37 至 3.86）。在比较 GLP1 受体激动剂组与 SGLT2 抑制剂组的额外分析中，甲状腺癌的风险比为 1.16（0.65 至 2.05）。结论 在这项使用来自三个国家的全国数据的大型队列研究中，在平均 3.9 年的随访期内，GLP1 受体激动剂的使用与甲状腺癌风险的大幅增加无关。在比较 GLP1 受体激动剂与 DPP4 抑制剂的主要分析中，置信区间的上限与相对风险增加不超过 31% 一致。没有其他可用数据。本研究分析的数据基于斯堪的纳维亚国家登记册。寄存器中的个人级别数据只能通过安全服务器访问，并且只允许导出研究文章中提出的聚合数据。只有在满足保护研究参与者的匿名性和其他数据安全问题的特定要求后，才能授予访问数据的许可。由于这些原因，数据无法普遍提供。