de Boer Rudolf A, Núñez Julio, Kozlovski Plamen, Wang Yi, Proot Pieter, Keefe Deborah
University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Servicio de Cardiología, Hospital Clínico Universitario Valencia, València, Spain.
Br J Clin Pharmacol. 2020 Jul;86(7):1346-1356. doi: 10.1111/bcp.14248. Epub 2020 Mar 10.
Explore the efficacy, safety and tolerability of the dual sodium-glucose cotransporter (SGLT) 1 and 2 inhibitor, licogliflozin in patients with type-2 diabetes mellitus (T2DM) and heart failure.
This multicentre, parallel-group phase IIA study randomized 125 patients with T2DM and heart failure (New York Heart Association II-IV; plasma N-terminal pro b-type natriuretic peptide [NT-proBNP] >300 pg/mL) to licogliflozin (2.5 mg, 10 mg, 50 mg) taken at bedtime, empagliflozin (25 mg) or placebo (44 patients completed the study). The primary endpoint was change from baseline in NT-proBNP after 12 weeks. Secondary endpoints included change from baseline in glycated haemoglobin, fasting plasma glucose, weight, blood pressure, fasting lipid profile, high-sensitivity c-reactive protein, and safety and tolerability.
Licogliflozin 10 mg for 12 weeks significantly reduced NT-proBNP vs placebo (Geometric mean ratio 0.56 [95% confidence interval: 0.33, 0.95], P = .033). A trend was observed with 50 mg licogliflozin (0.64 [95% confidence interval: 0.40, 1.03], P = .064), with no difference between licogliflozin and empagliflozin. The largest numerical decreases in glycated haemoglobin were with licogliflozin 50 mg (-0.58 ± 0.34%) and empagliflozin (-0.44 ± 1.18%) vs placebo (-0.04 ± 0.91%). The reduction in body weight was similar with licogliflozin 50 mg (-2.15 ± 2.40 kg) and empagliflozin (-2.25 ± 1.89 kg). A numerical reduction in systolic blood pressure was seen with licogliflozin 50 mg (-9.54 ± 16.88 mmHg) and empagliflozin (-6.98 ± 15.03 mmHg) vs placebo (-2.85 ± 11.97 mmHg). Adverse events (AEs) were mild, including hypotension (6.5%), hypoglycaemia (8.1%) and inadequate diabetes control (1.6%). The incidence of diarrhoea (4.9%) was lower than previously reported.
The reduction in NT-proBNP with licogliflozin suggests a potential benefit of SGLT1 and 2 inhibition in patients with T2DM and heart failure.
探讨双重钠-葡萄糖协同转运蛋白（SGLT）1和2抑制剂利格列净在2型糖尿病（T2DM）合并心力衰竭患者中的疗效、安全性和耐受性。
这项多中心、平行组IIA期研究将125例T2DM合并心力衰竭患者（纽约心脏协会II-IV级；血浆N末端B型利钠肽原[NT-proBNP]>300 pg/mL）随机分为睡前服用利格列净（2.5 mg、10 mg、50 mg）、恩格列净（25 mg）或安慰剂组（44例患者完成研究）。主要终点是12周后NT-proBNP相对于基线的变化。次要终点包括糖化血红蛋白、空腹血糖、体重、血压、空腹血脂谱、高敏C反应蛋白相对于基线的变化，以及安全性和耐受性。
利格列净10 mg服用12周相对于安慰剂显著降低了NT-proBNP（几何平均比0.56[95%置信区间：0.33，0.95]，P = 0.033）。观察到利格列净剂量为50 mg时有此趋势（0.64[95%置信区间：0.40，1.03]，P = 0.064），利格列净与恩格列净之间无差异。糖化血红蛋白数值下降最大的是利格列净50 mg组（-0.58±0.34%）和恩格列净组（-0.44±1.18%），而安慰剂组为（-0.04±0.91%）。利格列净50 mg组（-2.15±2.40 kg）和恩格列净组（-2.25±1.89 kg）体重减轻情况相似。利格列净50 mg组（-9.54±16.88 mmHg）和恩格列净组（-6.98±15.03 mmHg）收缩压有数值下降，而安慰剂组为（-2.85±11.97 mmHg）。不良事件（AE）为轻度，包括低血压（6.5%）、低血糖（8.1%）和糖尿病控制不佳（1.6%）。腹泻发生率（4.9%）低于先前报道。
利格列净降低NT-proBNP表明SGLT1和2抑制在T2DM合并心力衰竭患者中具有潜在益处。
