Impact of sodium-glucose cotransporter-2 inhibitors on the risk of hip fracture in older patients in Japan using a nationwide administrative claims database: A matched case-control study

Aim: Some clinical trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors are associated with fracture risk. However, this notion remains controversial. This study aimed to evaluate hip fracture risk after the use of SGLT2 inhibitors while controlling for factors that may affect fracture risk. Furthermore, hip fracture risk is evaluated in relation to the SGLT2 inhibitors component and its concomitant use with other antidiabetic agents. Methods: Using large-scale real-world data, this case-control study investigated hospitalized patients between January 2018 and December 2020. Patients were aged 65-89 years and had been prescribed with SGLT2 inhibitors at least twice. Patients with hip fracture (cases) and those without (controls) were identified via 1:3 matching according to sex, age (+/- 3 years), hospital size classification, and number of concomitant antidiabetic agents. Exposure to SGLT2 inhibitors of the cases and controls was compared with the use of multivariate conditional logistic regression. Results: After matching, 396 cases and 1081 controls were identified. The adjusted odds ratio for patients receiving treatment with SGLT2 inhibitors was 0.83 (95% confidence interval: 0.55-1.26), indicating no increase in hip fracture risk. Additionally, no increased risk was observed with respect to SGLT2 inhibitors by component or concomitant use with other antidiabetic agents. Conclusion: Our study showed that SGLT2 inhibitors do not increase hip fractures in older patients. However, because the risk assessment of SGLT2 inhibitors by component and their concomitant use with other antidiabetic agents is based on a limited number of patients, it is important to interpret the results with caution.