Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany.
Department of Biomedical Sciences, Panum Institute, NovoNordisk Foundation Center for Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Diabetes Obes Metab. 2017 Feb;19(2):200-207. doi: 10.1111/dom.12802. Epub 2016 Nov 9.
To determine whether the addition of sitagliptin to pre-existing therapy with liraglutide changes glycaemic excursions after a mixed meal.
A total of 16 patients with type 2 diabetes treated with metformin and liraglutide (1.2 mg/d for ≥2 weeks) were randomized (sealed envelopes), within a cross-over design, to be studied on two occasions, after an overnight fast, with (1) sitagliptin (100 mg orally) and (2) placebo (patients and care givers blinded) administered 60 minutes before a mixed meal, or vice versa. Glucose excursions (incremental area under the curve [AUC]; primary endpoint) and insulin, C-peptide, glucagon and incretin concentrations were measured. The study setting was a metabolic study unit at a specialized diabetes hospital.
All 16 patients completed the study and were analysed. Glucose (AUC 319 ± 30 [placebo] vs 315 ± 18 mmol.L .min [sitagliptin], Δ 7 [95% confidence interval -50 to 63] mmol.L .min ), insulin, C-peptide and glucagon concentrations were not affected significantly by sitagliptin treatment ( P = .60-1.00). Intact glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) concentrations were augmented by sitagliptin, by 78.4% and 90.2%, respectively (both P < .0001). The influence of sitagliptin treatment on incretin plasma concentrations was similar to previously published results obtained in patients with type 2 diabetes on metformin treatment only.
Sitagliptin, in patients already treated with a GLP-1 receptor agonist (liraglutide), increased intact GLP-1 and GIP concentrations, but with marginal, non-significant effects on glycaemic control. GLP-1 receptors have probably been maximally stimulated by liraglutide. Our findings do not support combination treatment with GLP-1 receptor agonists and DPP-4 inhibitors, but longer-term trials are needed to support clinical recommendations.
确定在给予混合餐之前，西格列汀与利拉鲁肽的预先存在的治疗联合是否改变餐后血糖波动。
总共纳入 16 例接受二甲双胍和利拉鲁肽（1.2 mg/d，至少 2 周）治疗的 2 型糖尿病患者，他们按照交叉设计，随机（密封信封）分为两组，在空腹过夜后分别接受西格列汀（100 mg 口服）和安慰剂（患者和护理人员设盲）治疗，在给予混合餐之前 60 分钟给药，或者反之。测量血糖波动（增量曲线下面积[AUC]；主要终点）和胰岛素、C 肽、胰高血糖素和肠促胰岛素浓度。研究场所是一家专门的糖尿病医院的代谢研究单元。
所有 16 例患者均完成了研究并进行了分析。与安慰剂组（AUC319±30mmol·L-1·min-1）相比，西格列汀组的血糖（AUC315±18mmol·L-1·min-1，Δ7mmol·L-1·min-1 [95%置信区间-50 至 63]）、胰岛素、C 肽和胰高血糖素浓度无显著变化（P=0.60-1.00）。西格列汀治疗使完整的胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性胰岛素释放肽（GIP）浓度分别增加 78.4%和 90.2%（均 P＜0.0001）。西格列汀治疗对肠促胰岛素血浆浓度的影响与先前在仅接受二甲双胍治疗的 2 型糖尿病患者中获得的结果相似。
在已经接受 GLP-1 受体激动剂（利拉鲁肽）治疗的患者中，西格列汀增加了完整的 GLP-1 和 GIP 浓度，但对血糖控制的影响轻微且无统计学意义。GLP-1 受体可能已被利拉鲁肽最大程度地刺激。我们的研究结果不支持 GLP-1 受体激动剂和 DPP-4 抑制剂的联合治疗，但需要进行更长期的试验来支持临床建议。
