Real-world risk of hypoglycemia-related hospitalization in Japanese patients with type 2 diabetes using SGLT2 inhibitors: a nationwide cohort study

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are believed to lower glucose levels and inhibit cardiovascular events related to type 2 diabetes (T2D). To maximize their benefits, the risk of resultant hypoglycemia has to be minimized; however, the magnitude of this risk remains unclear. Here, we aimed to identify clinical factors linked to an increased risk of hypoglycemia among Japanese patients with T2D and treated with SGLT2 inhibitors. RESEARCH DESIGN AND METHODS: This was a real-world retrospective cohort study conducted using the Japanese Medical Data Vision database. We identified patients with T2D and treated with SGLT2 inhibitors who were enrolled in the database from April 2014 to October 2019. Cox multivariate regression analyses were performed to determine demographical and clinical factors linked to SGLT2 inhibitor-associated hypoglycemia-related hospitalization. RESULTS: (HR 1.98; 95% CI 1.50 to 2.61), insulin use (HR 3.26; 95% CI 2.43 to 4.38), and sulfonylurea use (HR 1.44; 95% CI 1.02 to 2.03). The risk was lower in women than in men (HR 0.73; 95% CI 0.54 to 0.98) and low in concomitant metformin users (HR 0.52; 95% CI 0.37 to 0.74). CONCLUSIONS: These findings may help minimize the risk of hypoglycemia-related hospitalization due to T2D treatment with SGLT2 inhibitors. We revealed that the risk of hypoglycemia may be higher when combining SGLT2 inhibitors with sulfonylureas and/or insulin. Furthermore, we discovered a high risk of hypoglycemia in older and non-obese patients. These findings may assist in maximizing the benefits of SGLT2 inhibitors for the treatment of T2D.