Abstract
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 (<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. These findings add to the evidence base evaluating the potential risks associated with SGLT-2i use for older adults outside of randomized clinical trials.
Highlights
Older adults with type 2 diabetes (T2D) are at an increased risk of death from cardiovascular disease compared with older adults without T2D.1 Sodium-glucose cotransporter–2 inhibitors (SGLT-2i) are oral diabetes medications that reduce the risk of atherosclerotic cardiovascular events, hospitalization for heart failure, end-stage kidney disease, and death among adults with T2D.2-6 There is, a concern that sodium-glucose cotransporter–2 inhibitors (SGLT-2i) may be associated with an increased risk of fracture on the basis of findings in 1 randomized clinical trial (RCT).[7]
There was no difference in the risk of fracture in SGLT-2i users compared with dipeptidyl peptidase 4 inhibitor (DPP-4i) users (HR, 0.90; 95% CI, 0.73-1.11) or glucagon-like peptide 1 receptor agonist (GLP-1RA) users (HR, 1.00; 95% CI, 0.80-1.25)
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
Summary
Older adults with type 2 diabetes (T2D) are at an increased risk of death from cardiovascular disease compared with older adults without T2D.1 Sodium-glucose cotransporter–2 inhibitors (SGLT-2i) are oral diabetes medications that reduce the risk of atherosclerotic cardiovascular events, hospitalization for heart failure, end-stage kidney disease, and death among adults with T2D.2-6 There is, a concern that SGLT-2i may be associated with an increased risk of fracture on the basis of findings in 1 randomized clinical trial (RCT).[7]. Older adults with type 2 diabetes (T2D) are at an increased risk of death from cardiovascular disease compared with older adults without T2D.1. Sodium-glucose cotransporter–2 inhibitors (SGLT-2i) are oral diabetes medications that reduce the risk of atherosclerotic cardiovascular events, hospitalization for heart failure, end-stage kidney disease, and death among adults with T2D.2-6. There is, a concern that SGLT-2i may be associated with an increased risk of fracture on the basis of findings in 1 randomized clinical trial (RCT).[7] Together, T2D and aging may have negative effects on bone metabolism.[8,9,10] In addition, other comorbidities, such as osteoporosis and chronic kidney disease, increase the risk of fracture in older adults.[11,12,13] understanding the fracture risk associated with SGLT-2i in older adults with T2D is critical
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