Affiliation:
1. Diabetes and Metabolism Information Center, Research Institute National Center for Global Health and Medicine Tokyo Japan
2. Institute for Global Health Policy Research, Bureau of International Health Cooperation National Center for Global Health and Medicine Tokyo Japan
3. Department of Health Services Research, Institute of Medicine University of Tsukuba Ibaraki Japan
4. Health Services Research and Development Center University of Tsukuba Ibaraki Japan
5. Division of Health Services Research National Cancer Center Tokyo Japan
6. Department of Public Health/Health Policy, Graduate School of Medicine The University of Tokyo Tokyo Japan
7. Department of Diabetes, Endocrinology, and Metabolism National Center for Global Health and Medicine Tokyo Japan
8. Diabetes Research Center, Research Institute National Center for Global Health and Medicine Tokyo Japan
Abstract
ABSTRACTAims/IntroductionA 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 MethodsThis 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.ResultsSitagliptin 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.ConclusionsWe observed no evidence to suggest an increased cancer risk among patients prescribed NTTP‐contaminated sitagliptin, although continued investigation is needed.
Funder
Japan Health Research Promotion Bureau
Reference21 articles.
1. Trends in Diabetes Treatment and Control in U.S. Adults, 1999–2018
2. Retrospective nationwide study on the trends in first‐line antidiabetic medication for patients with type 2 diabetes in Japan
3. U.S. Food and Drug Administration.FDA works to avoid shortage of sitagliptin following detection of nitrosamine impurity.2022. Available from:https://www.fda.gov/drugs/drug‐safety‐and‐availability/fda‐works‐avoid‐shortage‐sitagliptin‐following‐detection‐nitrosamine‐impurityAccessed May 30 2024.
4. U.S. Food and Drug Administration.Control of nitrosamine Impurities in Human Drugs–Guidance for Industry.2021. Available from:https://www.fda.gov/media/141720/downloadAccessed May 30 2024.
5. History of the secondary use of national database of health insurance claims and specific health checkups of Japan (NDB);Kato G;Trans Jpn Soc Med Biol Eng,2017