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

被引:47
作者
Zhuo, Min [1 ,2 ,3 ,4 ]
Hawley, Chelsea E. [1 ,5 ]
Paik, Julie M. [1 ,2 ,3 ,6 ]
Bessette, Lily G. [1 ]
Wexler, Deborah J. [7 ]
Kim, Dae H. [1 ,8 ,9 ]
Tong, Angela Y. [1 ]
Kim, Seoyoung C. [1 ,3 ,10 ]
Patorno, Elisabetta [1 ]
机构
[1] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremt St,Ste 3030, Boston, MA 02120 USA
[2] Brigham & Womens Hosp, Dept Med, Div Renal Med, 75 Francis St, Boston, MA 02115 USA
[3] Harvard Med Sch, Boston, MA 02120 USA
[4] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02120 USA
[5] VA Bedford Healthcare Syst, New England Geriatr Res, Educ & Clin Ctr, Bedford, MA USA
[6] VA Boston Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA
[7] Harvard Med Sch, Diabet Ctr, Massachusetts Gen Hosp, Boston, MA 02120 USA
[8] Harvard Med Sch, Marcus Inst Aging Res, Hebrew Senior Life, Boston, MA 02120 USA
[9] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA
[10] Brigham & Womens Hosp, Dept Med, Div Rheumatol Inflammat & Immun, 75 Francis St, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
HIP-FRACTURES; FRAILTY; EVENTS; COHORT; SCORE; MODEL;
D O I
10.1001/jamanetworkopen.2021.30762
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
IMPORTANCE 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. OBJECTIVE 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). DESIGN, SETTING, AND PARTICIPANTS 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. EXPOSURES 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. MAIN OUTCOMES AND MEASURES 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. RESULTS 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). CONCLUSIONS AND RELEVANCE 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.
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页数:14
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