Initiation of dapagliflozin and treatment-emergent fractures

Research output: Contribution to journalArticlepeer-review


  • Konstantinos Toulis
  • John P Bilezikian
  • Wasim Hanif
  • Kalliopi Kotsa
  • Deepi Keerthy

External organisations

  • Columbia University in the City of New York
  • Queen Elizabeth Hospital Birmingham, Queen Elizabeth Medical Centre
  • Aristotle University of Thessaloniki


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.


Original languageEnglish
Pages (from-to)1070-1074
JournalDiabetes, obesity & metabolism
Issue number4
Early online date30 Nov 2017
Publication statusPublished - 8 Jan 2018