Initiation of dapagliflozin and treatment-emergent fractures

An increase in the fracture risk was reported in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin, possibly mediated by effects induced by all members of the sodium-glucose co-transporter 2 inhibitors (SGLT2i) class. It is unclear whether initiation of dapagliflozin is followed by an increase in the risk of fracture. Therefore, we performed a population-based, open cohort study was performed (January 2013-January 2016) using The Health Improvement Network (THIN). 22,618 patients with T2DM (4,548 exposed to dapagliflozin and 18,070 under standard antidiabetic treatment, matched for age and sex) with no history of fractures at baseline. The primary outcome was the occurrence of any fragility fracture during the observation period. Risk of any fracture served as a secondary outcome. Adjusted Hazard Rate Ratios (aHR) with 95% confidence intervals (CI) were calculated using Cox regression. A total of 289 fractures (132 fragility fractures) were recorded during the observation period. No difference in the risk of fragility fracture was detected between patients prescribed dapagliflozin and matched controls (Crude HR: 0.90, 95% CI: 0.59-1.39, p-value = 0.645 and adjusted HR: 0.87, 95% CI: 0.56-1.35, p-value = 0.531). Similarly, no difference in the risk of any fracture was detected (aHR: 0.89, 95% CI: 0.66-1.20, p-value =0.427). Sensitivity analyses limited to the subset of the population at high risk of fracture produced similar results. Thus, there was no evidence to suggest an increase in the risk of treatment-emergent fractures in patients with T2DM being initiated treatment with dapagliflozin.