Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m2 and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks’ treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m2, geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium–glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (–43.9% [95% confidence interval −54.7 to −30.6]) and 600 μg (−49.9% [−59.3 to −38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.

中文翻译：

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一项随机 2b 期试验检查了胰高血糖素样肽-1 和胰高血糖素受体激动剂 cotadutide 对糖尿病肾病患者肾脏结局的影响


Cotadutide 是一种胰高血糖素样肽-1 （GLP-1） 和胰高血糖素受体激动剂，可改善 2 型糖尿病 （T2D） 和慢性肾病 （CKD） 患者的肾功能。在这项 2b 期研究中，T2D 和 CKD 患者（估计肾小球滤过率 [eGFR] 为 20 或更高，且每 1.73 m2 低于 90 mL/min，尿白蛋白与肌酐比值 [UACR] 超过 50 mg/g）被随机分配 1：1：1：1：1：1 至 26 周治疗，接受标准治疗加皮下注射 cotadutide 滴定至 100、300 或 600 μg， 或安慰剂每日（双盲），或 GLP-1 激动剂索马鲁肽 1 mg，每周一次（开放标签）。共同主要终点是 UACR 从基线到第 14 周结束的绝对变化和与安慰剂相比的百分比变化。在 248 名随机分组的患者中，平均年龄 67.1 岁，19% 为女性，平均 eGFR 为 55.3 mL/min/1.73 m2，几何平均值为 UACR 205.5 mg/g（变异系数 270.0），46.8% 接受伴随钠-葡萄糖协同转运蛋白 2 抑制剂。从基线到第 14 周结束时，Cotadutide 剂量依赖性地降低了 UACR，与安慰剂相比，在 300 μg （-43.9% [95% 置信区间 -54.7 至 -30.6]）和 600 μg （-49.9% [-59.3 至 -38.4]）时达到显著性;效果在第 26 周持续。各组之间的严重不良事件是平衡的。cotadutide 600 μg 的安全性和耐受性与 semaglutide 相当。因此，我们的研究表明，在 T2D 和 CKD 患者中，cotadutide 在标准护理的基础上显着降低了 UACR，具有可接受的耐受性，这表明肾脏保护益处需要在更大规模的研究中得到证实。