The Association of SGLT2i vs DPP4i on Fracture: A Cohort Study in Veterans with Diabetes

Kathryn Snyder MD, MPH , Katherine Griffin MPH , Amber Hackstadt PhD , Amir Javid PhD , Adriana Hung MD, MPH , Robert Greevy PhD , Christianne L. Roumie MD, MPH
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Abstract

Background

Increased bone turnover is associated with use of SGLT2i. Patients with diabetes experience adverse effects on bone metabolism. Our aim was to evaluate if SGLT2i was associated with fractures vs DPP4i as add-on therapy to diabetes regimens.

Methods

We assembled a retrospective cohort of Veterans with diabetes combining Veterans Administration, Medicare, and National Death Index databases. Using an active comparator new user design, patients starting on SGLT2i or DPP4i were followed from prescription fill until a fracture event, death, stopping medication, loss of follow-up, or study end. Fractures included: face/skull, spine, ribs, long bones, hand/feet/digits, or hip. Fractures were identified based on a validated algorithm with positive predictive value 91.3% (86.8, 94.4). Cox models compared the association of fractures between SGLT2i and DPP4i in a propensity score-weighted cohort that balanced 70+ covariates including comorbidities, vital signs, labs, vitamin D levels, smoking, and medications.

Results

The unweighted sample included 115,124 SGLT2i episodes (104,086 Veterans; 94% empagliflozin; 4% canagliflozin; 2% dapagliflozin) and 213,095 DPP4i episodes (173,724 Veterans; 45% saxagliptin; 15% sitagliptin; 34% alogliptin; 6% Linagliptin). After propensity score calculation and matched weighting, the cohort included 76,072 SGLT2i and 75,833 DPP4i episodes. Median age was 69.3 years and diabetes duration 9.7 (6.1, 14.0) years. In the matched weighted analyses, there were 1431 and 1564 fractures among SGLT2i and DPP4i users, respectively. There were no clinical differences in fractures per 1000 person-years: 18.2 (17.4, 19.1) vs 19.8 (19.0, 20.6). The adjusted hazard ratio (adjusted hazard ratio 0.93 [0.87, 0.99]) excluded increased risk of fractures (adjusted hazard ratio > 1) in SGLT2i users.

Conclusions

SGLT2i use as add-on treatment for diabetes was not associated with increased fracture outcomes compared to DPP4i.

Abstract Image

SGLT2i与DPP4i与骨折的关系:一项糖尿病退伍军人的队列研究
背景:骨转换增加与SGLT2i的使用有关。糖尿病患者的骨代谢会受到不良影响。我们的目的是评估SGLT2i与DPP4i作为糖尿病治疗方案的附加治疗是否与骨折相关。方法:结合退伍军人管理局、联邦医疗保险和国家死亡指数数据库,对糖尿病退伍军人进行回顾性队列研究。采用主动比较新用户设计,开始使用SGLT2i或DPP4i的患者从处方开始随访,直到骨折事件、死亡、停药、失去随访或研究结束。骨折包括:面部/颅骨、脊柱、肋骨、长骨、手/脚/手指或臀部。基于经过验证的算法识别裂缝,阳性预测值为91.3%(86.8,94.4)。Cox模型在倾向评分加权队列中比较了SGLT2i和DPP4i之间骨折的相关性,该队列平衡了70多个协变量,包括合并症、生命体征、实验室、维生素D水平、吸烟和药物。结果未加权样本包括115,124例SGLT2i发作(104,086例退伍军人;empagliflozin 94%;canagliflozin 4%;2%达格列净)和213,095次DPP4i发作(173,724例退伍军人;saxagliptin 45%;sitagliptin 15%;alogliptin 34%;Linagliptin 6%)。经过倾向评分计算和匹配加权后,该队列包括76,072例SGLT2i和75,833例DPP4i发作。中位年龄为69.3岁,糖尿病病程为9.7(6.1,14.0)年。在匹配加权分析中,SGLT2i和DPP4i使用者中分别有1431例和1564例骨折。每1000人年骨折发生率无临床差异:18.2 (17.4,19.1)vs 19.8(19.0, 20.6)。调整风险比(调整风险比0.93[0.87,0.99])排除骨折风险增加(调整风险比>;1)在SGLT2i用户中。结论:与DPP4i相比,ssglt2i作为糖尿病的附加治疗与骨折结局增加无关。
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来源期刊
American journal of medicine open
American journal of medicine open Medicine and Dentistry (General)
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