There are concerns that sodium-glucose co-transporter 2 inhibitors (SGLT2Is) may increase the risk of fractures in patients with type 2 diabetes. To date, large cardiovascular outcome trials have generated conflicting findings, and few real-world studies have been conducted to assess this association. As fracture risk in this vulnerable population is associated with increased mortality, there is an urgent need to address this safety issue using real-world data. Thus, the objective of this population-based cohort study is to determine if use of SGLT2Is is associated with an increased fracture risk in patients with type 2 diabetes. Using the UK Clinical Practice Research Datalink, a large primary care database, we identified a cohort of patients newly treated with antihyperglycemic drugs between January 2013 and December 2017. Use of SGLT2Is was modeled as a time-varying exposure and compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4Is). Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs of incident fractures associated with use of SGLT2Is overall and according to specific SGLT2Is (dapagliflozin, empagliflozin, canagliflozin). We conducted several sensitivity analyses to address potential sources of bias. The cohort included 73,178 patients, which generated 153,179 person-years of observation. During follow-up, 1,973 patients were newly diagnosed with fractures (incidence rate: 12.9/1000 per year). Compared with DPP-4Is, SGLT2Is were not associated with an increased risk of fracture (HR: 0.97, 95% CI: 0.79-1.19). Similar findings were observed when stratifying on specific SGLT2Is, with HRs ranging between 0.67 and 1.42, with all CIs including the null value. The sensitivity analyses yielded highly consistent findings. The results of this large population-based study suggest that use of SGLT2Is is not associated with fracture incidence. This finding should provide reassurance on the safety of this class of drugs.
D. Abrahami: None. A. Douros: None. H. Yin: None. O. Yu: None. L. Azoulay: None.
Canadian Institutes of Health Research