Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
J Diabetes Investig. 2022 Jan;13(1):54-64. doi: 10.1111/jdi.13624. Epub 2021 Aug 3.
AIMS/INTRODUCTION: The sodium-glucose cotransporter 2 inhibitor, canagliflozin, reduced kidney failure and cardiovascular events in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. We carried out a post-hoc analysis to evaluate the efficacy and safety of canagliflozin in a subgroup of participants in East and South-East Asian (EA) countries who are at high risk of renal complications.
Participants with an estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m and urinary albumin-to-creatinine ratio of >300-5,000 mg/g were randomized to 100 mg of canagliflozin or a placebo. The effects of canagliflozin treatment on pre-specified efficacy and safety outcomes were examined using Cox proportional hazards regression between participants from EA countries (China, Japan, Malaysia, the Philippines, South Korea and Taiwan) and the remaining participants.
Of 4,401 participants, 604 (13.7%) were from EA countries; 301 and 303 were assigned to the canagliflozin and placebo groups, respectively. Canagliflozin lowered the risk of primary outcome (composite of end-stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) in EA participants (hazard ratio 0.54, 95% confidence interval 0.35-0.84). The effects of canagliflozin on renal and cardiovascular outcomes in EA participants were generally similar to those of the remaining participants. Safety outcomes were similar between the EA and non-EA participants.
In the CREDENCE trial, the risk of renal and cardiovascular events was safely reduced in participants from EA countries at high risk of renal events.
目的/引言：钠-葡萄糖共转运蛋白 2 抑制剂卡格列净可减少衰竭和心血管事件的发生在卡格列净和肾脏事件在糖尿病与既定肾病临床评估（CREDENCE）试验。我们进行了一项事后分析，以评估卡格列净在东亚和东南亚（EA）国家高风险肾病并发症的参与者亚组中的疗效和安全性。
估计肾小球滤过率为 30 至 <90 ml/min/1.73 m 和尿白蛋白/肌酐比值> 300-5000 mg/g 的参与者被随机分配到 100 mg 卡格列净或安慰剂组。使用 Cox 比例风险回归法比较来自 EA 国家（中国、日本、马来西亚、菲律宾、韩国和中国台湾）和其余参与者的参与者之间的卡格列净治疗对预先指定的疗效和安全性结果的影响。
在 4401 名参与者中，604 名（13.7%）来自 EA 国家；301 名和 303 名分别被分配到卡格列净和安慰剂组。卡格列净降低了 EA 参与者主要结局（终末期肾病、血清肌酐水平加倍、肾脏或心血管死亡的复合结局）的风险（风险比 0.54，95%置信区间 0.35-0.84）。卡格列净对 EA 参与者的肾脏和心血管结局的影响与其余参与者的影响大致相似。安全性结果在 EA 和非 EA 参与者之间相似。
在 CREDENCE 试验中，高风险肾病事件的 EA 国家参与者的肾脏和心血管事件风险得到了安全降低。
