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

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.

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.

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.

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.