在患有 2 型糖尿病和 3a/3b 期 CKD 的患者中，贝格列净的安全性和有效性。
Safety and Effectiveness of Bexagliflozin in Patients With Type 2 Diabetes Mellitus and Stage 3a/3b CKD.
机构信息
Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA.
Translational Medicine Group, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA; Shanghai JiaYue PharmaTech, Shanghai, China.
出版信息
Am J Kidney Dis. 2019 Sep;74(3):328-337. doi: 10.1053/j.ajkd.2019.03.417. Epub 2019 May 14.
RATIONALE & OBJECTIVE: Hyperglycemia exacerbates the progression of chronic kidney disease (CKD), but most glucose-lowering therapies do not address morbidities associated with CKD. Sodium/glucose cotransporter 2 (SGLT2) inhibitors offer potential benefits to patients with diabetes and CKD, but their effectiveness may be diminished with decreased kidney function. We aimed to evaluate the safety and effectiveness of bexagliflozin, a novel SGLT2 inhibitor, in patients with type 2 diabetes and CKD.
STUDY DESIGN
Phase 3, double-blind, placebo-controlled, multicenter, multinational, randomized trial.
SETTING & PARTICIPANTS: 54 sites across 4 countries. Patients with CKD stage 3a or 3b, type 2 diabetes mellitus, and hemoglobin A level of 7.0% to 10.5% and estimated glomerular filtration rate (eGFR) of 30 to 59mL/min/1.73m who were taking oral hypoglycemic agents for 8 weeks.
INTERVENTIONS
Bexagliflozin, 20mg, daily versus placebo for 24 weeks.
OUTCOMES
Primary outcome was change in percent hemoglobin A from baseline to week 24. Secondary end points included changes in body weight, systolic blood pressure, albuminuria, and hemoglobin A level stratified by CKD stage.
RESULTS
312 patients across 54 sites were analyzed. Bexagliflozin lowered hemoglobin A levels by 0.37% (95% CI, 0.20%-0.54%); P<0.001 compared to placebo. Patients with CKD stages 3a (eGFR, 45-<60mL/min/1.73m) and 3b (eGFR, 30-<45mL/min/1.73m) experienced reductions in hemoglobin A levels of 0.31% (P=0.007) and 0.43% (P=0.002), respectively. Bexagliflozin decreased body weight (1.61kg; P<0.001), systolic blood pressure (3.8mm Hg; P=0.02), fasting plasma glucose level (0.76mmol/L; P=0.003), and albuminuria (geometric mean ratio reduction of 20.1%; P=0.03). Urinary tract infection and genital mycotic infections were more common in the bexagliflozin group; otherwise, frequencies of adverse events were comparable between groups.
LIMITATIONS
Not designed to evaluate the impact of treatment on long-term kidney disease and cardiovascular outcomes.
CONCLUSIONS
Bexagliflozin reduces hemoglobin A levels in patients with diabetes and stage 3a/3b CKD and appears to be well tolerated. Additional observed benefits included reductions in body weight, systolic blood pressure, and albuminuria.
FUNDING
Trial was sponsored by Theracos Sub, LLC.
背景与目的
高血糖会加重慢性肾脏病（CKD）的进展，但大多数降血糖疗法并不能解决与 CKD 相关的并发症。钠/葡萄糖共转运蛋白 2（SGLT2）抑制剂为糖尿病合并 CKD 患者带来了潜在益处，但随着肾功能下降，其疗效可能会降低。我们旨在评估新型 SGLT2 抑制剂贝格列净在 2 型糖尿病合并 CKD 患者中的安全性和有效性。
研究设计
这是一项 3 期、双盲、安慰剂对照、多中心、多国、随机临床试验。
地点和参与者
来自 4 个国家的 54 个地点。患者为 CKD 3a 期或 3b 期、2 型糖尿病、血红蛋白 A1c 水平为 7.0%10.5%，估算肾小球滤过率（eGFR）为 3059mL/min/1.73m²，接受口服降糖药治疗 8 周。
干预措施
每日服用贝格列净 20mg，或安慰剂，治疗 24 周。
主要结局
从基线到第 24 周时血红蛋白 A 的百分比变化。次要终点包括按 CKD 分期分层的体重、收缩压、白蛋白尿和血红蛋白 A 水平的变化。
结果
54 个地点的 312 名患者纳入分析。与安慰剂相比，贝格列净使血红蛋白 A 水平降低了 0.37%（95%CI，0.20%0.54%）；P<0.001。CKD 3a 期（eGFR，45<60mL/min/1.73m）和 3b 期（eGFR，30~<45mL/min/1.73m）患者的血红蛋白 A 水平分别降低了 0.31%（P=0.007）和 0.43%（P=0.002）。贝格列净降低了体重（1.61kg；P<0.001）、收缩压（3.8mmHg；P=0.02）、空腹血糖水平（0.76mmol/L；P=0.003）和白蛋白尿（几何均数比值降低 20.1%；P=0.03）。贝格列净组更常见尿路感染和生殖器霉菌感染；否则，两组间不良事件的发生率相当。
局限性
未设计用于评估治疗对长期肾脏疾病和心血管结局的影响。
结论
贝格列净可降低 2 型糖尿病合并 3a/3b CKD 患者的血红蛋白 A 水平，且似乎具有良好的耐受性。其他观察到的益处包括体重、收缩压和白蛋白尿的降低。
资金来源
该试验由 Theracos Sub，LLC 赞助。
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