Boston, MA: Study on SGLT2 Inhibitors and Fracture Risk

A recent study in the JAMA Network Open has shown that the initiation of SGLT2 inhibitors does not appear to increase the risk of fracture in older adults with type 2 diabetes versus other diabetes agents.

Older adults with type 2 diabetes (T2D) are known to be at a higher risk of death from cardiovascular disease compared to their peers without T2D. Sodium-glucose cotransporter–2 inhibitors (SGLT-2i) are oral diabetes medications that reduce the risk of end-stage kidney disease, atherosclerotic cardiovascular events, hospitalization for heart failure, and death among adults with T2D. However, results from previous studies have shown SGLT-2i to be associated with increased fracture risk.

Based on the above background, Min Zhuo, Harvard Medical School, Boston, Massachusetts, and colleagues aimed 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).

For this purpose, the researchers performed a population-based, new-user cohort study including older adults with T2D enrolled in Medicare fee-for-service from April 2013 to December 2017. 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.

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 age, 72 years; 64,126 men [47%]) matched 1:1:1 for analyses.

Based on the study, the researchers found no difference in the risk of fracture in SGLT-2i users compared with DPP-4i users (HR, 0.90) or GLP-1RA users (HR, 1.00). These results were found to be consistent across categories of sex, frailty (non-frail, prefrail, and frail), age (<75 and ≥75 years), and insulin use (baseline users and nonusers).

"In this nationwide Medicare cohort, initiating an SGLT-2i was not associated with an increased risk of fracture in older adults with T2D compared with initiating a DPP-4i or GLP-1RA, with consistent results across categories of frailty, age, and insulin use," the researchers wrote. "These findings add to the evidence base evaluating the potential risks associated with SGLT-2i use for older adults outside of randomized clinical trials."

Reference

Zhuo M, Hawley CE, Paik JM, et al. Association of Sodium-Glucose Cotransporter–2 Inhibitors With Fracture Risk in Older Adults With Type 2 Diabetes. JAMA Netw Open. 2021;4(10):e2130762. doi:10.1001/jamanetworkopen.2021.30762