Kitada Munehiro, Tsuda Shin-Ichi, Konishi Kazunori, Takeda-Watanabe Ai, Fujii Mizue, Kanasaki Keizo, Nishizawa Makoto, Nakagawa Atsushi, Koya Daisuke
Department of Diabetology and Endocrinology, Kanazawa Medical University, Ishikawa, Japan.
Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
BMJ Open Diabetes Res Care. 2017 Jul 7;5(1):e000391. doi: 10.1136/bmjdrc-2017-000391. eCollection 2017.
The objective of this study is to elucidate the effect of anagliptin on glucose/lipid metabolism and renoprotection in patients with type 2 diabetic nephropathy.
Twenty-five patients with type 2 diabetic nephropathy received anagliptin 200 mg/day for 24 weeks, and 20 patients who were switched to anagliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors were analyzed regarding primary and secondary endpoints. The primary endpoint was change in hemoglobin A1c (HbA1c) during treatment with anagliptin. Additionally, we evaluated changes in lipid data (low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglyceride), blood pressure (BP), urinary albumin to creatinine ratio (UACR), liver-type fatty acid-binding protein to creatinine ratio (ULFABP) and renal function (estimated glomerular filtration rate and serum cystatin C) as secondary endpoints.
After switching to anagliptin from other DPP-4 inhibitors, the levels of HbA1c in the 20 participants showed no significant change, 7.5%±1.2% at 24 weeks compared with 7.3%±0.9% at baseline. The levels of the log10-transformed UACR were significantly reduced from 1.95±0.51 mg/g creatinine (Cr) at baseline to 1.76±0.53 mg/g Cr at 24 weeks after anagliptin treatment (p<0.01). The percentage change in the UACR (Δ%UACR) from baseline to 24 weeks was also significantly lower by -10.6% (p<0.001). Lipid data, systolic BP and renal function were not changed during anagliptin treatment. Additionally, ULFABP in eight participants, who had ≥5 µg/g Cr at baseline, was significantly decreased from baseline (8.5±2.8 µg/g Cr) to 24 weeks (3.1±1.7 µg/g Cr, p<0.01) after anagliptin treatment, and the percentage change in the ULFABP during anagliptin treatment was -58.1% (p<0.001).
Anagliptin induced no significant change in HbA1c, lipid data, systolic BP and renal function. However, anagliptin reduced the UACR and ULFABP, although without a corresponding change in HbA1c, indicating direct action of anagliptin on renoprotection in patients with type 2 diabetic nephropathy.
本研究旨在阐明阿格列汀对2型糖尿病肾病患者糖脂代谢及肾脏保护作用的影响。
25例2型糖尿病肾病患者接受阿格列汀200mg/天治疗24周，对20例从其他二肽基肽酶-4（DPP-4）抑制剂转换为阿格列汀治疗的患者进行主要和次要终点分析。主要终点为阿格列汀治疗期间糖化血红蛋白（HbA1c）的变化。此外，我们评估了脂质数据（低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和甘油三酯）、血压（BP）、尿白蛋白肌酐比值（UACR）、肝型脂肪酸结合蛋白肌酐比值（ULFABP）和肾功能（估算肾小球滤过率和血清胱抑素C）的变化作为次要终点。
从其他DPP-4抑制剂转换为阿格列汀治疗后，20例参与者的HbA1c水平无显著变化，24周时为7.5%±1.2%，而基线时为7.3%±0.9%。经阿格列汀治疗24周后，对数转换后的UACR水平从基线时的1.95±0.51mg/g肌酐（Cr）显著降至1.76±0.53mg/g Cr（p<0.01）。从基线到24周UACR的百分比变化（Δ%UACR）也显著降低了-10.6%（p<0.001）。在阿格列汀治疗期间，脂质数据、收缩压和肾功能未发生变化。此外，在基线时ULFABP≥5μg/g Cr的8例参与者中，经阿格列汀治疗后，ULFABP从基线时的（8.5±2.8μg/g Cr）显著降至24周时的（3.1±1.7μg/g Cr，p<0.01），阿格列汀治疗期间ULFABP的百分比变化为-58.1%（p<0.001）。
阿格列汀对HbA1c、脂质数据、收缩压和肾功能无显著影响。然而，阿格列汀降低了UACR和ULFABP，尽管HbA1c没有相应变化，这表明阿格列汀对2型糖尿病肾病患者具有直接的肾脏保护作用。
