Do sodium-glucose cotransporter 2 inhibitors lead to fracture risk? A pharmacovigilance real-world study.

AIMS/INTRODUCTION: Given the mechanism of action of sodium-glucose cotransporter 2 inhibitors (SGLT2is), these drugs can also reduce bone density and increase fracture risk. We aimed to identify and characterize fracture-related adverse events that are associated with SGLT2is. MATERIALS AND METHODS: In this observational, retrospective, pharmacovigilance, real-world study, we used disproportionality and Bayesian analyses to compare fracture-related adverse event reporting in patients who received SGLT2is from the first quarter in 2004 to the fourth quarter in 2019 in the Food and Drug Administration Adverse Event Reporting System. We also compared the effect on combined therapy with SGLT2is and other glucose-lowering medications (GLMs), and compared their onset times and outcomes. RESULTS: A total of 317 SGLT2is-associated fractures were identified. Affected patients tended to be aged >45 years (68.76%) and were more often male than female (58.04% vs 34.07%). SGLT2is-associated fracture is most commonly reported with canagliflozin (51.10%), dapagliflozin (24.60%) and empagliflozin (23.66%). SGLT2is or SGLT2is combined with GLMs do not show an association with fracture risk under disproportionality and Bayesian analyses. SGLT2i-associated fractures result in hospitalization in 66.64% of patients and death in 9.38% of patients. GLMs show an increased hospitalization rate compared with SGLT2is (69.72% vs 55.14%, P < 0.0001) and GLMs plus SGLT2is (69.72% vs 61.20%, P = 0.0197). CONCLUSIONS: Based on the Food and Drug Administration Adverse Event Reporting System database, no association is noted between fracture risk and SGLT2is, or SGLT2is combined with GLMs. Long-term follow up and high-quality studies need to further verify and explore the relationship between SGLT2is and fractures.