Seasonality of drug-related hypoglycemia in Japan: A study using spontaneous reporting system data

Abstract Hypoglycemia is a common issue in diabetes pharmacotherapy, with seasonal variations potentially influencing its occurrence. It has been reported that blood glucose levels exhibit seasonal variation, suggesting that seasonal factors may influence the occurrence of hypoglycemia. In this study, we examined the seasonal patterns of drug-related hypoglycemia according to causative drug categories using the Japanese Adverse Drug Event Report database. We assessed a total of 545,012 adverse event reports submitted between December 2004 and November 2024, among which 5332 cases of drug-related hypoglycemia were identified. The results indicated a consistent increase in hypoglycemia reports during the winter months, with the lowest percentage observed in August (0.78%), followed by a gradual rise, reaching a peak in February (1.13%). Diabetic medications, including sulfonylureas, alpha-glucosidase inhibitors, and thiazolidinediones, showed an increased frequency of hypoglycemia signals in winter. Some non-diabetic medications, such as fluoroquinolones and angiotensin II receptor blockers, exhibited similar seasonal trends. These findings suggest that seasonal factors may warrant consideration in the prevention of drug-related hypoglycemia.