Sodium–glucose cotransporter 2 inhibitors do not increase the risk of fractures in real-world clinical practice in Korea: A national observational cohort study

Abstract

AIMS/INTRODUCTION: This study aimed to determine whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) were related to increased fracture risk in adults with type 2 diabetes compared with dipeptidyl peptidase-4 inhibitors (DPP-4i). MATERIALS AND METHODS: Between 1 May 2016 and 31 December 2018, we carried out a new-user cohort study using the Korean National Health Insurance Service database. Propensity score matching was carried out on 478,826 new users of an SGLT2i or DPP-4i. After propensity score matching on >80 covariates, 84,460 individuals were initiated on SGLT2i or DPP-4i, with 42,230 individuals in each treatment group. The time to first fracture event was compared between the SGLT2i and DPP-4i groups using Cox proportional hazards models, and the results are reported as hazard ratios with 95% confidence intervals for fracture occurrence. Subgroup analyses investigated fractures between treatment groups according to baseline characteristics. RESULTS: Individuals who were started on SGLT2i were not linked with increased fracture risk in both as-treated and intention-to-treat analyses (as-treated: hazard ratio 0.98, 95% confidence interval 0.92-1.04; intention-to-treat: hazard ratio 0.94, 95% confidence interval 0.89-1.00). We identified no significant interaction between the individuals' age, sex, fracture history or thiazolidinedione use in any subgroup analyses, showing that none of these variables appeared to be impact modifiers in the connection between SGLT2i and fractures. CONCLUSIONS: Our study found no increase in the risk of fracture among individuals treated with SGLT2i in a real-world clinical setting for type 2 diabetes.