Abstract
AIMS/INTRODUCTION: We aimed to clarify the real-world risk of lower-limb amputation and identify factors related to increased risk in Japanese patients with type 2 diabetes using sodium-glucose cotransporter 2 inhibitors (SGLT2is). MATERIALS AND METHODS: We carried out a retrospective observational cohort study utilizing the Japanese Medical Data Vision, a diagnosis procedure combination database. We identified 107,296 patients with type 2 diabetes who were initiated on SGLT2is or metformin (control; n = 53,648 per group) using 1:1 propensity score matching from April 2014 to October 2019. The hazard ratio (HR) for the risk of lower-limb amputation was analyzed using a Cox proportional hazards model adjusted for patients' baseline characteristics and use of concomitant medical agents. RESULTS: Of the 107,296 patients, 66 (0.06%); that is, 41 (0.08%) in the SGLT2is group and 25 (0.05%) in the metformin group, underwent amputation, with no significant difference in the proportions between the groups. There was no significant difference in the risk of amputation between the SGLT2is and metformin groups (HR 1.34, 95% confidence interval [CI] 0.80-2.24). However, female sex (HR 2.78, 95% CI 1.12-6.94) and use of strong statins (HR 2.68; 95% CI 1.18-8.20) were significantly associated with a higher risk of amputation in the SGLT2is group than in the metformin group. CONCLUSIONS: SGLT2is might not be related to an increased risk of lower-limb amputation in patients with type 2 diabetes in real-world clinical practice. The possible increased risk of SGLT2is-associated amputation in female patients with type 2 diabetes and patients with type 2 diabetes requiring strong statins is notable.