Watts Nelson B, Bilezikian John P, Usiskin Keith, Edwards Robert, Desai Mehul, Law Gordon, Meininger Gary
Mercy Health Osteoporosis and Bone Health Services Clinical Trial Center (N.B.W.), Cincinnati, Ohio 45236; Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; and Janssen Research & Development, LLC (K.U., R.E., M.D., G.L., G.M.), Raritan, New Jersey 08869.
J Clin Endocrinol Metab. 2016 Jan;101(1):157-66. doi: 10.1210/jc.2015-3167. Epub 2015 Nov 18.
Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).
The purpose of this study was to describe the effects of canagliflozin on bone fracture risk.
This was a randomized phase 3 study in patients with T2DM.
Canagliflozin doses of 100 and 300 mg were evaluated in the overall population of patients from 9 placebo- and active-controlled studies (N = 10 194), as well as in separate analyses of a single trial enriched with patients with a prior history/risk of cardiovascular disease (ie, the CANagliflozin cardioVascular Assessment Study [CANVAS]; N = 4327) and a pooled population of 8 non-CANVAS studies (N = 5867).
The incidence of adjudicated fracture adverse events (AEs), fall-related AEs, and volume depletion-related AEs was assessed.
The incidence of fractures was similar with canagliflozin (1.7%) and noncanagliflozin (1.5%) in the pooled non-CANVAS studies. In CANVAS, a significant increase in fractures was seen with canagliflozin (4.0%) vs placebo (2.6%) that was balanced between the upper and lower limbs. The incidence of fractures was higher with canagliflozin (2.7%) vs noncanagliflozin (1.9%) in the overall population, which was driven by the increase of fractures in CANVAS. The incidence of reported fall-related AEs was low, but significantly higher with canagliflozin in CANVAS, potentially related to volume depletion-related AEs, but not significantly different in the pooled non-CANVAS studies and the overall population.
Fracture risk was increased with canagliflozin treatment, driven by CANVAS patients, who were older, with a prior history/risk of cardiovascular disease, and with lower baseline estimated glomerular filtration rate and higher baseline diuretic use. The increase in fractures may be mediated by falls; however, the cause of increased fracture risk with canagliflozin is unknown.
卡格列净是一种开发用于治疗2型糖尿病（T2DM）的钠-葡萄糖协同转运蛋白2抑制剂。
本研究旨在描述卡格列净对骨折风险的影响。
这是一项针对T2DM患者的随机3期研究。
在来自9项安慰剂对照和活性对照研究的患者总体人群（N = 10194）中评估了100毫克和300毫克剂量的卡格列净，同时在一项单独分析中评估了一项纳入有心血管疾病既往史/风险患者的单一试验（即卡格列净心血管评估研究[CANVAS]；N = 4327）以及8项非CANVAS研究的汇总人群（N = 5867）。
评估经判定的骨折不良事件（AE）、跌倒相关AE和容量耗竭相关AE的发生率。
在汇总的非CANVAS研究中，卡格列净组（1.7%）和非卡格列净组（1.5%）的骨折发生率相似。在CANVAS研究中，卡格列净组（4.0%）的骨折发生率显著高于安慰剂组（2.6%），且上下肢骨折发生率均衡。在总体人群中，卡格列净组（2.7%）的骨折发生率高于非卡格列净组（1.9%），这是由CANVAS研究中骨折发生率的增加所驱动。报告的跌倒相关AE发生率较低，但在CANVAS研究中卡格列净组显著更高，可能与容量耗竭相关AE有关，但在汇总的非CANVAS研究和总体人群中无显著差异。
卡格列净治疗会增加骨折风险，这是由CANVAS研究中的患者驱动的，这些患者年龄较大，有心血管疾病既往史/风险，基线估计肾小球滤过率较低且基线利尿剂使用量较高。骨折增加可能由跌倒介导；然而，卡格列净导致骨折风险增加的原因尚不清楚。
