(P-294) Risk of Fracture Associated with SGLT-2 Inhibitors as an Add-on Therapy to Metformin in Patients with Type 2 Diabetes Mellitus

Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitor is an anti-diabetic drug which decreases the blood glucose level by promoting urinary excretion of glucose. Regarding this, the safety issues have been concerned that the use of dapagliflozin is associated with the risk of fracture in patients with type 2 diabetes mellitus (T2DM) and moderate renal impairment.

Objectives: To evaluate the association between SGLT-2 inhibitors use and the risk of fracture as an add-on therapy to metformin in patients with T2DM compared to dipeptidyl peptidase-4 (DPP-4) inhibitors and sulfonylurea (SU) in Korean population.

Methods: We conducted a retrospective cohort study using the National Health Insurance Service database in Korea from 2012 to 2018. Patients aged ≥ 40 years and those diagnosed with T2DM prior to drug prescription were enrolled in this study. The outcome was osteoporotic fracture. Analysis was performed using Cox’s proportional hazard model following 1:1 propensity score matching to calculate the hazard ratio (HR) with a 95% confidence interval (CI).

Results: A total of 13,023, 12,868 patients were assigned to the DPP-4 inhibitors, SU comparator groups, respectively. There was not associated with the use SGLT-2 inhibitors and the risk of osteoporotic fracture than DPP-4 inhibitors (HR: 0.86, 95% CI: 0.68–1.07) and SU (HR: 0.75, 95% CI: 0.61-0.94), as an add-on therapy to metformin. As a result of analyzing in patients who treated with dapagliflozin or had moderate renal impairment, we found no statistically differences.

Conclusions: In this study of patients with T2DM, SGLT-2 inhibitors as an add-on therapy to metformin was not associated with increased risk of osteoporotic fracture. However, it is necessary to closely monitor when prescribing SGLT-2 inhibitors in long-term study of patients with T2DM and moderate renal impairment.