Association of Sodium-Glucose Cotransporter-2 Inhibitors With Fracture Risk in Older Adults With Type 2 Diabetes

• Published in: JAMA network open 2021-10, Vol.4 (10), p.e2130762-e2130762
• Main Authors: Zhuo, Min, Hawley, Chelsea E, Paik, Julie M, Bessette, Lily G, Wexler, Deborah J, Kim, Dae H, Tong, Angela Y, Kim, Seoyoung C, Patorno, Elisabetta
• Format: Article
• Language: English
• Subjects: Aged; Clinical trials; Cohort Studies; Diabetes; Diabetes and Endocrinology; Diabetes Mellitus, Type 2 - drug therapy; Female; Fractures; Fractures, Bone - etiology; GLP-1 receptor agonists; Humans; Male; Medicare; Middle Aged; Older people; Online Only; Original Investigation; Osteoporosis; Risk Assessment; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; United States
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2021.30762

Whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are associated with an increased risk of fractures in older adults with type 2 diabetes (T2D) outside of clinical trials remains unknown. To examine the association of incident fracture among older adults with T2D with initiating an SGLT-2i compared with initiating a dipeptidyl peptidase 4 inhibitor (DPP-4i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA). This is a population-based, new-user cohort study including older adults (aged ≥65 years) with T2D enrolled in Medicare fee-for-service from April 2013 to December 2017. Data analysis was performed from October 2020 to April 2021. New users of an SGLT-2i, DPP-4i, or GLP-1RA without a previous fracture were matched in a 1:1:1 ratio using 3-way propensity score matching. The primary outcome was a composite end point of nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention within 30 days. After 3-way 1:1:1 propensity score matching, multivariable Cox proportional hazards regression models were used to generate hazard ratios (HRs) for SGLT-2i compared with DPP-4i and GLP-1RA and Kaplan-Meier curves to visualize fracture risk over time across groups. Of 466 933 new initiators of study drugs, 62 454 patients were new SGLT-2i users. After 3-way matching, 45 889 (73%) new SGLT-2i users were matched to new users of DPP-4i and GLP-1RA, yielding a cohort of 137 667 patients (mean [SD] age, 72 [5] years; 64 126 men [47%]) matched 1:1:1 for analyses. There was no difference in the risk of fracture in SGLT-2i users compared with DPP-4i users (HR, 0.90; 95% CI, 0.73-1.11) or GLP-1RA users (HR, 1.00; 95% CI, 0.80-1.25). Results were consistent across categories of sex, frailty (nonfrail, prefrail, and frail), age (