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. 2024 Dec 3;14(1):30072.
doi: 10.1038/s41598-024-81698-z.

A retrospective study of seasonal variation in sodium-glucose co-transporter 2 inhibitor-related adverse events using the Japanese adverse drug event report database

Kiyoka Matsumoto  1 , Fumiya Goto  1 , Mika Maezawa  1 , Satoshi Nakao  1   2 , Koumi Miyasaka  1 , Sakiko Hirofuji  1 , Kohei Shiota  1 , Nanaka Ichihara  1 , Moe Yamashita  1 , Yuka Nokura  1 , Tomofumi Yamazaki  1 , Kana Sugishita  1 , Hideyuki Tanaka  1 , Hirofumi Tamaki  3 , Motoyuki Ishiguro  4 , Kazuhiro Iguchi  3 , Mitsuhiro Nakamura  5
Affiliations

A retrospective study of seasonal variation in sodium-glucose co-transporter 2 inhibitor-related adverse events using the Japanese adverse drug event report database

Kiyoka Matsumoto et al. Sci Rep. .

Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a class of drugs used in the clinical management of patients with type 2 diabetes, and their prescriptions have been increasing in recent years. Herein, we performed a retrospective analysis of seasonal variation in SGLT2 inhibitor-associated adverse events recorded in the Japanese Adverse Drug Event Report (JADER) database, an adverse event reporting database which reflects real-world clinical practice. To this end, seasonal variations in SGLT2 inhibitor-related dehydration, cerebral infarction, urinary tract infection, and ketoacidosis were analyzed. Six SGLT2 inhibitors prescribed in Japan (ipragliflozin, empagliflozin, luseogliflozin, canagliflozin, dapagliflozin, and tofogliflozin) were included. The reporting ratio (RR) for SGLT2 inhibitor adverse events per month in the JADER database from April 2014 to December 2023 was determined. The RR for dehydration-related adverse events was highest in the summer months of July and August, as well as in the winter months of December, January, and February. The highest RR for cerebral infarction was in February. No association with seasonal variations in the occurrence of ketoacidosis related to dehydration was observed. Healthcare providers should take adequate precautions against dehydration caused by SGLT2 inhibitors, not only in summer but also in winter. These findings are instructive and informational for health care professionals involved in diabetes care.

Keywords: Adverse events; Dehydration; Seasonal variation; Sodium-glucose co-transporter 2 inhibitors; Type 2 diabetes mellitus.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Ethical approval was not sought for this study because the study was a database-related observational study which did not directly involve any research subjects. All results were obtained from data openly available online from the PMDA website ( www.pmda.go.jp ). All data from the JADER database were fully anonymized by the relevant regulatory authority before we accessed them. Our research does not fall within the purview of any of the following laws and guidelines: “Clinical Trials Act (Act No. 16 of April 14, 2017),” “Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Law number: Act No. 145 of 1960, Last Version: Amendment of Act No. 50 of 2015),” “Guideline for good clinical practice E6 (R1), https://www.pmda.go.jp/int-activities/int-harmony/ich/0076.html ,” “Ethical guidelines for human genome and gene analysis research, https://www.mhlw.go.jp/general/seido/kousei/i-kenkyu/genome/0504sisin.html ,” and “Ethical Guidelines for Medical and Health Research Involving Human Subjects, https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/hokabunya/kenkyujigyou/i-kenkyu/index.html .” Therefore, it is not subject to ethical examination. The study was an observational study without any research subjects. No consent to participate was required due to the retrospective nature of this study.

Figures

Fig. 1
Fig. 1
Flowchart of analysis.
Fig. 2
Fig. 2
Lader chart of the reporting ratio of SGLT2 inhibitor-related adverse events and average temperatures in Japan.
See this image and copyright information in PMC

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