Apperloo Ellen M, Gorriz Jose L, Soler Maria Jose, Cigarrán Guldris Secundino, Cruzado Josep M, Puchades Maria Jesús, López-Martínez Marina, Waanders Femke, Laverman Gozewijn D, van der Aart-van der Beek Annemarie, Hoogenberg Klaas, van Beek André P, Verhave Jacobien, Ahmed Sofia B, Schmieder Roland E, Wanner Christoph, Cherney David Z I, Jongs Niels, Heerspink Hiddo J L
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Nephrology, University Clinical Hospital, INCLIVA, University of Valencia, Valencia, Spain.
Nat Med. 2025 Jan;31(1):278-285. doi: 10.1038/s41591-024-03327-6. Epub 2024 Oct 25.
Semaglutide reduces albuminuria and the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease (CKD). We conducted a randomized placebo-controlled double-blind clinical trial in adults with CKD (estimated glomerular filtration rate (eGFR) ≥25 ml min 1.73 m and urine albumin-to-creatinine ratio (UACR) ≥30 and <3,500 mg g) and body mass index ≥27 kg m. Participants were randomized to semaglutide 2.4 mg per week or placebo. The primary endpoint was percentage change from baseline in UACR at week 24. Safety was monitored throughout. Overall, 125 participants were screened, of whom 101 were randomized to semaglutide (n = 51) or placebo (n = 50). Mean age was 55.8 (s.d. 12) years; 40 participants (39.6%) were female; median UACR was 251 mg g (interquartile range 100, 584); mean eGFR was 65.0 (s.d. 25) ml min 1.73 m; and mean body mass index was 36.2 (s.d. 5.6) kg m. Chronic glomerulonephritis (n = 25) and hypertensive CKD (n = 27) were the most common CKD etiologies. Treatment for 24 weeks with semaglutide compared to placebo reduced UACR by -52.1% (95% confidence interval -65.5, -33.4; P < 0.0001). Gastrointestinal adverse events were more often reported with semaglutide (n = 30) than with placebo (n = 15). Semaglutide treatment for 24 weeks resulted in a clinically meaningful reduction in albuminuria in patients with overweight/obesity and non-diabetic CKD. ClinicalTrials.gov registration: NCT04889183 .
司美格鲁肽可降低2型糖尿病合并慢性肾脏病（CKD）患者的蛋白尿及肾病进展风险。我们对估算肾小球滤过率（eGFR）≥25 ml·min⁻¹·1.73 m²且尿白蛋白与肌酐比值（UACR）≥30且<3500 mg/g、体重指数≥27 kg/m²的成年CKD患者进行了一项随机、安慰剂对照、双盲临床试验。参与者被随机分为每周注射2.4 mg司美格鲁肽组或安慰剂组。主要终点为第24周时UACR较基线的百分比变化。全程监测安全性。总体而言，共筛查了125名参与者，其中101名被随机分配至司美格鲁肽组（n = 51）或安慰剂组（n = 50）。平均年龄为55.8（标准差12）岁；40名参与者（39.6%）为女性；UACR中位数为251 mg/g（四分位间距100, 584）；平均eGFR为65.0（标准差25）ml·min⁻¹·1.73 m²；平均体重指数为36.2（标准差5.6）kg/m²。慢性肾小球肾炎（n = 25）和高血压性CKD（n = 27）是最常见的CKD病因。与安慰剂相比，司美格鲁肽治疗24周可使UACR降低-52.1%（95%置信区间-65.5, -33.4；P < 0.0001）。司美格鲁肽（n = 30）比安慰剂（n = 15）更常报告胃肠道不良事件。司美格鲁肽治疗24周可使超重/肥胖且非糖尿病性CKD患者的蛋白尿出现具有临床意义的降低。ClinicalTrials.gov注册号：NCT04889183 。
