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Abstract：
Chronic kidney disease (CKD) is a common complication of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and lower body weight in people with T2D, and some reduce the risk of cardiovascular (CV) events in those with high CV risk. GLP-1RAs might also have kidney-protective effects. We report the design and baseline data for FLOW (NCT03819153), a trial investigating the effects of semaglutide, a once-weekly (OW) GLP-1RA, on kidney outcomes in participants with CKD and T2D.
FLOW is a randomised, double-blind, parallel-group, multinational, phase 3b trial. Participants with T2D, estimated glomerular filtration rate (eGFR) ≥50‒≤75 ml/min/1.73 m2 and urine albumin:creatinine ratio (UACR) >300‒<5000 mg/g or eGFR ≥25‒<50 ml/min/1.73 m2 and UACR >100‒<5000 mg/g were randomised 1:1 to OW semaglutide 1.0 mg or matched placebo, with renin-angiotensin-aldosterone system blockade (unless not tolerated/contraindicated). The composite primary endpoint is time to first kidney failure (persistent eGFR <15 ml/min/1.73 m2 or initiation of chronic kidney replacement therapy), persistent ≥50% reduction in eGFR or death from kidney or CV causes.
Enrolled participants (N = 3534) had a baseline mean age of 66.6 years [standard deviation (SD) 9.0], haemoglobin A1c of 7.8% (SD 1.3), diabetes duration of 17.4 years (SD 9.3), eGFR of 47.0 ml/min/1.73 m2 (SD 15.2) and median UACR of 568 mg/g (range 2‒11 852). According to Kidney Disease: Improving Global Outcomes guidelines categorisation, 68.2% were at very high risk for CKD progression.
FLOW will evaluate the effect of semaglutide on kidney outcomes in participants with CKD and T2D, and is expected to be completed in late 2024.
FLOW is a randomised, double-blind, parallel-group, multinational, phase 3b trial. Participants with T2D, estimated glomerular filtration rate (eGFR) ≥50‒≤75 ml/min/1.73 m2 and urine albumin:creatinine ratio (UACR) >300‒<5000 mg/g or eGFR ≥25‒<50 ml/min/1.73 m2 and UACR >100‒<5000 mg/g were randomised 1:1 to OW semaglutide 1.0 mg or matched placebo, with renin-angiotensin-aldosterone system blockade (unless not tolerated/contraindicated). The composite primary endpoint is time to first kidney failure (persistent eGFR <15 ml/min/1.73 m2 or initiation of chronic kidney replacement therapy), persistent ≥50% reduction in eGFR or death from kidney or CV causes.
Enrolled participants (N = 3534) had a baseline mean age of 66.6 years [standard deviation (SD) 9.0], haemoglobin A1c of 7.8% (SD 1.3), diabetes duration of 17.4 years (SD 9.3), eGFR of 47.0 ml/min/1.73 m2 (SD 15.2) and median UACR of 568 mg/g (range 2‒11 852). According to Kidney Disease: Improving Global Outcomes guidelines categorisation, 68.2% were at very high risk for CKD progression.
FLOW will evaluate the effect of semaglutide on kidney outcomes in participants with CKD and T2D, and is expected to be completed in late 2024.
摘要：
背景：慢性肾脏病（CKD）是2型糖尿病（T2D）的常见并发症。胰高血糖素样肽-1受体激动剂（GLP-1RAs）改善T2D患者的血糖控制和降低体重，和一些降低心血管（CV）风险高的人的风险。GLP-1RA也可能具有肾脏保护作用。我们报告了FLOW的设计和基准数据，一项试验调查了每周一次(OW)GLP-1RA司美鲁肽对CKD和T2D参与者肾脏结局的影响.
方法：FLOW是随机的，双盲,平行组，跨国公司,3b期试验。T2D参与者，估计的肾小球滤过率（eGFR）≥50-≤75mL/min/1.73m2和尿白蛋白与肌酐比率（UACR）>300-<5,000mg/g或eGFR≥25-<50mL/min/1.73m2和UACR>100-<5,000mg/g，以1：1随机分配给OWsemaglutide1.0mg或匹配的安慰剂，肾素-血管紧张素-醛固酮系统阻断（除非不耐受/禁忌）。复合主要终点是时间到第一：肾衰竭（持续eGFR<15mL/min/1.73m²或开始慢性肾脏替代疗法）;持续≥50％的eGFR降低;或因肾脏或CV原因死亡。
结果：注册参与者（N=3.534）的基线平均（SD）年龄为66.6（9.0）岁，HbA1c为7.8（1.3）％，糖尿病持续时间为17.4（9.3）年，eGFR为47.0（15.2）mL/min/1.73m2，中位UACR为568（范围：2-11.852）mg/g。根据肾脏疾病：改善全球结果指南分类，68.2%的患者有非常高的CKD进展风险。
结论：FLOW将评估司马鲁肽对CKD和T2D患者肾脏结局的影响，预计将于2024年底完成。
方法：FLOW是随机的，双盲,平行组，跨国公司,3b期试验。T2D参与者，估计的肾小球滤过率（eGFR）≥50-≤75mL/min/1.73m2和尿白蛋白与肌酐比率（UACR）>300-<5,000mg/g或eGFR≥25-<50mL/min/1.73m2和UACR>100-<5,000mg/g，以1：1随机分配给OWsemaglutide1.0mg或匹配的安慰剂，肾素-血管紧张素-醛固酮系统阻断（除非不耐受/禁忌）。复合主要终点是时间到第一：肾衰竭（持续eGFR<15mL/min/1.73m²或开始慢性肾脏替代疗法）;持续≥50％的eGFR降低;或因肾脏或CV原因死亡。
结果：注册参与者（N=3.534）的基线平均（SD）年龄为66.6（9.0）岁，HbA1c为7.8（1.3）％，糖尿病持续时间为17.4（9.3）年，eGFR为47.0（15.2）mL/min/1.73m2，中位UACR为568（范围：2-11.852）mg/g。根据肾脏疾病：改善全球结果指南分类，68.2%的患者有非常高的CKD进展风险。
结论：FLOW将评估司马鲁肽对CKD和T2D患者肾脏结局的影响，预计将于2024年底完成。
