SGLT2i use and fracture risk compared with DPP4i in patients with T2DM.

INTRODUCTION: The association between sodium-glucose cotransporter-2 inhibitor (SGLT2i) use and fracture risk remains inconclusive. Most previous studies have focused on treatment-naïve patients, despite many patients in routine clinical practice initiating SGLT2i therapy after prior dipeptidyl peptidase-4 inhibitor (DPP4i) use. This study aimed to evaluate the risk of fractures associated with SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) in Taiwan. MATERIALS AND METHODS: This nationwide cohort study used Taiwan's National Health Insurance Research Database. Patients with T2DM initiating SGLT2i or DPP4i therapy between 2016 and 2019 were identified. Follow-up began one year after the index date to ensure adequate treatment exposure before outcome assessment. A prevalent new-user design and 1:2 propensity score matching (PSM) were applied to balance baseline characteristics. Fractures were ascertained from medical claims, and competing risk regression was used to estimate fracture risk, accounting for death as a competing event. RESULTS: After PSM, 106,992 SGLT2i users and 213,984 DPP4i users were included with comparable baseline profiles. Over a mean follow-up of 3.5 years, the overall risk of any fracture did not differ between groups. Although SGLT2i use was associated with a significantly lower risk of hip fracture compared with DPP4i use (subdistribution hazard ratio = 0.89, 95% CI: 0.81-0.98), this association was no longer statistically significant after adjustment for multiple comparisons. Subgroup analyses yielded generally consistent findings. CONCLUSIONS: In this cohort, SGLT2i use was not associated with increased overall or major osteoporotic fracture risk vs DPP4i. The prevalent new-user design captures prior treatment histories and reflects real-world practice.