Assessment of cancer risk associated with 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine-contaminated sitagliptin use: A retrospective cohort study

IF 3.1 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Investigation Pub Date : 2024-08-12 DOI:10.1111/jdi.14281

Takehiro Sugiyama, Takashi Furuno, Yuichi Ichinose, Masao Iwagami, Noriko Ihana-Sugiyama, Kenjiro Imai, Tamaki Kakuwa, Ryoko Rikitake, Mitsuru Ohsugi, Takahiro Higashi, Hiroyasu Iso, Kohjiro Ueki

{"title":"Assessment of cancer risk associated with 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine-contaminated sitagliptin use: A retrospective cohort study","authors":"Takehiro Sugiyama, Takashi Furuno, Yuichi Ichinose, Masao Iwagami, Noriko Ihana-Sugiyama, Kenjiro Imai, Tamaki Kakuwa, Ryoko Rikitake, Mitsuru Ohsugi, Takahiro Higashi, Hiroyasu Iso, Kohjiro Ueki","doi":"10.1111/jdi.14281","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims/Introduction</h3>\n \n <p>A recent US Food and Drug Administration report highlighted concerns over nitrosamine (7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine [NTTP]) impurities in sitagliptin, prompting investigations into its safety profile. The present study aimed to determine if the use of NTTP-contaminated sitagliptin, in comparison with other dipeptidyl peptidase-4 (DPP-4) inhibitors, is associated with an increased cancer risk.</p>\n </section>\n \n <section>\n \n <h3> Materials and Methods</h3>\n \n <p>This retrospective cohort study secondarily used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing data on >120 million individuals. The study involved patients who initiated DPP-4 inhibitor therapy (sitagliptin or other DPP-4 inhibitors) and continued its exclusive use for 3 years. Sitagliptin users were compared with other DPP-4 inhibitor users for assessing the occurrence of cancers, as defined by diagnosis codes. Further analyses focused on specific types of cancer, using either diagnosis codes or a combination of diagnosis and procedure codes. We also carried out various sensitivity analyses, including those with different exposure periods.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Sitagliptin users (149,120 patients, 388,356 person-years) experienced 9,643 cancer incidences (2,483.0/100,000 person-years) versus 12,621 incidences (2,504.4/100,000 person-years) among other DPP-4 inhibitor users (199,860 patients, 503,952 person-years), yielding a minimal difference (incidence rate ratio 0.99, 95% confidence interval 0.97–1.02). A multiple Cox proportional hazards model showed no significant association between sitagliptin use and overall cancer incidence (hazard ratio 1.01, 95% confidence interval 0.98–1.04). Findings were also consistent across cancer types and sensitivity analyses.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>We observed no evidence to suggest an increased cancer risk among patients prescribed NTTP-contaminated sitagliptin, although continued investigation is needed.</p>\n </section>\n </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14281","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Diabetes Investigation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jdi.14281","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Aims/Introduction

A recent US Food and Drug Administration report highlighted concerns over nitrosamine (7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine [NTTP]) impurities in sitagliptin, prompting investigations into its safety profile. The present study aimed to determine if the use of NTTP-contaminated sitagliptin, in comparison with other dipeptidyl peptidase-4 (DPP-4) inhibitors, is associated with an increased cancer risk.

Materials and Methods

This retrospective cohort study secondarily used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing data on >120 million individuals. The study involved patients who initiated DPP-4 inhibitor therapy (sitagliptin or other DPP-4 inhibitors) and continued its exclusive use for 3 years. Sitagliptin users were compared with other DPP-4 inhibitor users for assessing the occurrence of cancers, as defined by diagnosis codes. Further analyses focused on specific types of cancer, using either diagnosis codes or a combination of diagnosis and procedure codes. We also carried out various sensitivity analyses, including those with different exposure periods.

Results

Sitagliptin users (149,120 patients, 388,356 person-years) experienced 9,643 cancer incidences (2,483.0/100,000 person-years) versus 12,621 incidences (2,504.4/100,000 person-years) among other DPP-4 inhibitor users (199,860 patients, 503,952 person-years), yielding a minimal difference (incidence rate ratio 0.99, 95% confidence interval 0.97–1.02). A multiple Cox proportional hazards model showed no significant association between sitagliptin use and overall cancer incidence (hazard ratio 1.01, 95% confidence interval 0.98–1.04). Findings were also consistent across cancer types and sensitivity analyses.

Conclusions

We observed no evidence to suggest an increased cancer risk among patients prescribed NTTP-contaminated sitagliptin, although continued investigation is needed.

Abstract Image

查看原文本刊更多论文

与使用受西他列汀污染的 7-亚硝基-3-(三氟甲基)-5,6,7,8-四氢[1,2,4] 三唑并[4,3-a]吡嗪相关的癌症风险评估：一项回顾性队列研究。

目的/引言：美国食品和药物管理局最近的一份报告强调了对西他列汀中亚硝胺（7-亚硝基-3-(三氟甲基)-5,6,7,8-四氢[1,2,4]三唑并[4,3-a]吡嗪[NTTP]）杂质的担忧，从而引发了对其安全性的调查。本研究旨在确定与其他二肽基肽酶-4（DPP-4）抑制剂相比，使用受 NTTP 污染的西他列汀是否与癌症风险增加有关：这项回顾性队列研究主要使用了日本全国健康保险索赔和特定健康检查数据库，其中包含超过 1.2 亿人的数据。研究涉及开始接受DPP-4抑制剂治疗（西他列汀或其他DPP-4抑制剂）并持续3年独家使用的患者。西他列汀使用者与其他DPP-4抑制剂使用者进行了比较，以评估癌症发生率，癌症发生率由诊断代码定义。进一步的分析侧重于特定类型的癌症，使用诊断代码或诊断与手术代码的组合。我们还进行了各种敏感性分析，包括不同暴露期的分析：结果：西他列汀使用者（149,120 名患者，388,356 人-年）的癌症发病率为 9,643 例（2,483.0/100,000 人-年），而其他 DPP-4 抑制剂使用者（199,860 名患者，503,952 人-年）的发病率为 12,621 例（2,504.4/100,000 人-年），两者差异极小（发病率比为 0.99，95% 置信区间为 0.97-1.02）。多重 Cox 比例危险模型显示，西他列汀的使用与癌症总发病率之间没有显著关联（危险比 1.01，95% 置信区间 0.98-1.04）。不同癌症类型和敏感性分析的结果也一致：我们没有观察到证据表明处方受 NTTP 污染的西他列汀的患者患癌症的风险会增加，但仍需继续调查。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Diabetes Investigation ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

9.40%

发文量

218

审稿时长

6-12 weeks

期刊介绍： Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).