Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, Denmark.
Diabetes Obes Metab. 2010 Apr;12(4):323-33. doi: 10.1111/j.1463-1326.2009.01167.x.
To examine the effects of 12 weeks of treatment with the DPP-4 inhibitor, sitagliptin, on gastrointestinal hormone responses to a standardized mixed meal and beta cell secretory capacity, measured as glucose and non-glucose induced insulin secretion during a hyperglycaemic clamp, in patients with type 2 diabetes.
A double-blinded, placebo-controlled study over 12 weeks in which 24 patients with T2DM were randomized to receive either sitagliptin (Januvia) 100 mg qd or placebo as an add-on therapy to metformin. In week 0, 1 and 12 patients underwent a meal test and a 90-min 20 mM hyperglycaemic clamp with 5 g of l-arginine infusion. Main outcome measure was postprandial total glucagon-like peptide 1 (GLP-1) concentration. Additional measures were insulin and C-peptide, glycaemic control, intact and total peptide YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP), and intact glucagon-like peptide 2 (GLP-2) and GLP-1.
All patients [sitagliptin n = 12, age: 59.5 (39-64) years, HbA1c: 8.0 (7.3-10.0)%, BMI: 33.2 (29.3-39.4); placebo n = 12, age: 60 (31-72) years, HbA1c: 7.7 (7.1-9.8)%, BMI: 30.7 (25.7-40.5)] [median (range)] completed the trial. Sitagliptin treatment improved glycaemic control, had no effect on total GLP-1, GIP or intact GLP-2, but reduced total PYY and PYY(3- 36), and increased PYY(1- 36) and intact incretin hormones. Sitagliptin improved first and second phases of beta cell secretion and maximal secretory capacity. All effects were achieved after 1 week. No significant changes occurred in the placebo group.
The postprandial responses of total GLP-1 and GIP and intact GLP-2 were unaltered. PYY degradation was prevented. Glucose and non-glucose induced beta cell secretion was improved. There was no difference in responses to sitagliptin between 1 and 12 weeks of treatment.
研究 12 周 DPP-4 抑制剂西他列汀（Sitagliptin）治疗对 2 型糖尿病（T2DM）患者混合餐胃肠激素反应及胰岛β细胞分泌功能（高血糖钳夹试验中葡萄糖和非葡萄糖刺激胰岛素分泌）的影响。
这是一项为期 12 周的双盲、安慰剂对照研究，24 例 T2DM 患者随机分为西他列汀（捷诺维，Januvia）100mg，qd 组或安慰剂组，作为二甲双胍的附加治疗。在第 0、1 和 12 周时，患者接受餐食试验和 90min 20mM 高血糖钳夹试验，同时输注 5g L-精氨酸。主要观察指标为餐后总胰高血糖素样肽 1（GLP-1）浓度。其他观察指标包括胰岛素和 C 肽、血糖控制、完整和总肽 YY（PYY）及葡萄糖依赖性胰岛素释放肽（GIP）和完整胰高血糖素样肽 2（GLP-2）和 GLP-1。
所有患者（西他列汀组 12 例，年龄 59.5（39-64）岁，糖化血红蛋白（HbA1c）8.0（7.3-10.0）%，BMI 33.2（29.3-39.4）；安慰剂组 12 例，年龄 60（31-72）岁，HbA1c 7.7（7.1-9.8）%，BMI 30.7（25.7-40.5））[中位数（范围）]完成了试验。西他列汀治疗改善了血糖控制，对总 GLP-1、GIP 或完整 GLP-2 无影响，但降低了总 PYY 和 PYY（3-36），增加了 PYY（1-36）和完整肠促胰岛素激素。西他列汀改善了胰岛β细胞分泌的第一和第二阶段及最大分泌能力。所有这些效果在治疗 1 周后均出现。安慰剂组无显著变化。
餐后总 GLP-1 和 GIP 及完整 GLP-2 反应无改变。PYY 降解被阻止。葡萄糖和非葡萄糖刺激的胰岛β细胞分泌功能得到改善。西他列汀治疗 1 周和 12 周的效果无差异。
