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

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

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.

MeSH terms

  • Adverse Drug Reaction Reporting Systems / statistics & numerical data
  • Aged
  • Benzhydryl Compounds / adverse effects
  • Canagliflozin / adverse effects
  • Databases, Factual
  • Dehydration / chemically induced
  • Diabetes Mellitus, Type 2* / drug therapy
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • East Asian People
  • Female
  • Glucosides / adverse effects
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Seasons*
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Sorbitol / adverse effects
  • Sorbitol / analogs & derivatives
  • Thiophenes / adverse effects
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / epidemiology

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucosides
  • dapagliflozin
  • Canagliflozin
  • empagliflozin
  • ipragliflozin
  • Benzhydryl Compounds
  • 6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
  • Sorbitol
  • Thiophenes
  • 1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol