Diabetes Trials Unit, University of Oxford, Oxford, U.K.
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
Diabetes Care. 2019 Jun;42(6):1075-1080. doi: 10.2337/dc18-2028. Epub 2019 Apr 22.
Increases in serum calcitonin, a tumor marker for medullary thyroid carcinoma (MTC), have been associated with glucagon-like peptide 1 receptor agonist use in some preclinical studies. We report calcitonin changes in exenatide-treated and placebo-administered participants and MTC incidence in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) and consider the impact of within-trial calcitonin monitoring.
EXSCEL participants were randomized 1:1 to once-weekly exenatide 2 mg or placebo. Serum calcitonin was measured at baseline (with trial medication discontinued if >40 ng/L) and annually thereafter (with trial medication discontinued if ≥50 ng/L). Median calcitonin concentrations were calculated at each time point, and thyroid malignancies were collected prospectively. Data regarding follow-up after an elevated calcitonin were collected retrospectively.
At baseline, 52 (30 exenatide and 22 placebo) participants had calcitonin >40 ng/L, and during follow-up an additional 23 participants (15 exenatide and 8 placebo) had calcitonin ≥50 ng/L in the intention-to-treat population. Median calcitonin concentrations were similar between treatment groups at baseline with no increase over time. Confirmed MTC occurred in three participants (2 exenatide and 1 placebo), all of whom had significantly elevated baseline calcitonin values (413, 422, and 655 ng/L).
During a median 3.2 years' follow-up, no change in serum calcitonin was seen with exenatide therapy. The three confirmed cases of MTC all occurred in participants with markedly elevated baseline calcitonin levels, measured prior to trial medication administration. Regular calcitonin monitoring identified no additional cases of MTC, suggesting no benefit of routine calcitonin monitoring during exenatide treatment.
在一些临床前研究中，血清降钙素水平的升高与胰高血糖素样肽 1 受体激动剂的使用有关，降钙素是甲状腺髓样癌（MTC）的肿瘤标志物。我们报告了艾塞那肽治疗组和安慰剂组参与者的降钙素变化情况，以及 EXSCEL 试验中 MTC 的发病率，并考虑了试验内降钙素监测的影响。
EXSCEL 参与者按 1:1 随机分配至每周一次艾塞那肽 2mg 或安慰剂。在基线时（如果 >40ng/L，则停止试验药物）和此后每年测量血清降钙素（如果≥50ng/L，则停止试验药物）。计算每个时间点的降钙素中位数浓度，并前瞻性收集甲状腺恶性肿瘤。回顾性收集了关于升高的降钙素后随访的数据。
在基线时，52 名（30 名艾塞那肽和 22 名安慰剂）参与者的降钙素>40ng/L，在随访期间，意向治疗人群中另有 23 名参与者（15 名艾塞那肽和 8 名安慰剂）的降钙素≥50ng/L。基线时，治疗组之间的降钙素中位数浓度相似，且随时间无增加。在 3 名参与者（2 名艾塞那肽和 1 名安慰剂）中确诊为 MTC，他们的降钙素基线值均显著升高（413、422 和 655ng/L）。
在中位数 3.2 年的随访期间，艾塞那肽治疗并未导致血清降钙素发生变化。所有 3 例确诊的 MTC 均发生在基线降钙素水平明显升高的参与者中，这些值是在开始试验药物治疗前测量的。定期监测降钙素并未发现更多的 MTC 病例，提示在艾塞那肽治疗期间常规监测降钙素并无获益。
