Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study
Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study
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DOI：
10.1185/03007990802418851
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发表时间：
2008-01-01
影响因子：
2.3
通讯作者：
MacConell, Leigh
中科院分区：
文献类型：
--
作者：
DeFronzo, Ralph A.;Okerson, Ted;MacConell, Leigh
背景资料：本研究评价了GLP-1受体激动剂艾塞那肽和DPP-4抑制剂西格列汀对T2 D患者餐后2小时血糖（PPG）、胰岛素和胰高血糖素分泌、胃排空和热量摄入的影响。HbA（1c）：8.5 ± 1.2%; 2小时PPG：245 ± 65 mg/dL。患者接受艾塞那肽（5 μ g BID持续1周，然后10 μ g BID持续1周）或西格列汀（100 mg QAM）持续2周。2周后，患者交叉接受替代治疗。通过标准膳食试验评估餐后血糖测量值;通过随意晚餐评估热量摄入（患者亚组）。通过对乙酰氨基酚吸收评估胃排空（Clinicaltrials.gov注册号：NCT 00477581）。结果：治疗2周后，艾塞那肽组2小时PPG低于西格列汀组：133 +/- 6 mg/dL vs 208 +/- 6 mg/dL，p < 0.0001（可评估，N = 61）。从依塞那肽转换为西格列汀使2小时PPG增加+73 +/- 11 mg/dL，而从西格列汀转换为依塞那肽使2小时PPG进一步降低+/- 76 +/- 10 mg/dL。艾塞那肽组的餐后血糖参数（AUC、C-ave、C-max）低于西格列汀组（p < 0.0001），空腹血糖下降幅度与艾塞那肽组和西格列汀组相似（-15 +/- 4 mg/dL vs. -19 +/- 4 mg/dL，p = 0.3234）。与西格列汀相比，依塞那肽改善了胰岛素分泌的胰岛素生成指数（艾塞那肽与西格列汀的比值：1.50 +/- 0.26，p = 0.0239），餐后胰高血糖素降低（艾塞那肽与西格列汀的AUC比值：0.88 +/- 0.03，p = 0.0011），餐后甘油三酯降低（艾塞那肽与西格列汀的AUC比：0.90 +/- 0.04，p = 0.0118）和胃排空减慢（对乙酰氨基酚艾塞那肽与西格列汀的AUC比：0.56 +/- 0.05，p < 0.0001）。与西格列汀相比，艾塞那肽降低了总热量摄入（-134 +/- 97 kcal vs. +130 +/- 97 kcal，p = 0.0227，N = 25）。两种治疗的常见不良事件是轻度至中度的强度和胃肠道的nature.Conclusions：虽然这项研究是有限的2周的曝光时间，这些数据表明，艾塞那肽有：（i）更大的影响比西格列汀降低餐后血糖和（ii）更有效的影响，以增加胰岛素分泌和减少餐后胰高血糖素分泌的T2 D患者。与西格列汀相比，依塞那肽可减缓胃排空并减少热量摄入。这些关键发现区分了两种基于肠促胰岛素的方法的治疗作用，并可能具有有意义的临床意义。
Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients.Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54% female; BMI: 33 +/- 5 kg/m(2); HbA(1c): 8.5 +/- 1.2%; 2-h PPG: 245 +/- 65 mg/dL. Patients received exenatide (5 mu g BID for 1 week, then 10 mu g BID for 1 week) or sitagliptin (100 mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581).Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133 +/- 6 mg/dL versus 208 +/- 6 mg/dL, p < 0.0001 (evaluable, N = 61). Switching from exenatide to sitagliptin increased 2-h PPG by +73 +/- 11 mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by +/- 76 +/- 10 mg/dL. Postprandial glucose parameters (AUC, C-ave, C-max) were lower with exenatide than sitagliptin (p < 0.0001).Reduction in fasting glucose was similar with exenatide and sitagliptin (-15 +/- 4 mg/dL vs. -19 +/- 4 mg/dL, p = 0.3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50 +/- 0.26, p = 0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88 +/- 0.03, p = 0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90 +/- 0.04, p = 0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56 +/- 0.05, p < 0.0001). Exenatide reduced total caloric intake compared to sitagliptin (-134 +/- 97 kcal vs. +130 +/- 97 kcal, p = 0.0227, N = 25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature.Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.