Feinglos M N, Saad M F, Pi-Sunyer F X, An B, Santiago O
Duke University Medical Center, Durham, NC 27710, USA.
Diabet Med. 2005 Aug;22(8):1016-23. doi: 10.1111/j.1464-5491.2005.01567.x.
Liraglutide (NN2211) is a long-acting GLP-1 analogue, with a pharmacokinetic profile suitable for once-daily administration. This multicentre, double-blind, parallel-group, double-dummy study explored the dose-response relationship of liraglutide effects on bodyweight and glycaemic control in subjects with Type 2 diabetes.
Subjects (BMI 27-42 kg/m(2)) with Type 2 diabetes who were previously treated with an OAD (oral anti-diabetic drug) monotherapy (69% with metformin), and had HbA(1c) < or = 10% were enrolled. After a 4-week metformin run-in period, 210 subjects (27-73 years, 60% female) were randomised to receive liraglutide (0.045-0.75 mg) once daily or continued on metformin 1000 mg b.d. for 12 weeks.
Mean baseline values for the six treatment groups ranged from 6.8 to 7.5% for HbA(1c), and 8.06-9.44 mmol/l (145-170 mg/dl) for fasting plasma glucose. After 12-week treatment, a weight change of -0.05 to -1.9% was observed for the six treatment groups. Mean HbA(1c) changes from baseline for 0.045, 0.225, 0.45, 0.6, 0.75 mg liraglutide and metformin were +1.28%, +0.86%, +0.22%, +0.16%, +0.30% and +0.09%, respectively. No significant differences in HbA(1c) were observed between liraglutide and metformin groups at the three highest liraglutide dose levels (0.45, 0.6 and 0.75 mg). The lowest two liraglutide doses (0.045 mg and 0.225 mg) were not sufficient to maintain the fasting plasma glucose values achieved by metformin. No major hypoglycaemic episodes were reported. Episodes of nausea and/or vomiting were reported by 11 patients (6.3%) receiving liraglutide and three (8.8%) receiving metformin.
Once-daily liraglutide improved glycaemic control and weight, in a comparable degree to metformin. Liraglutide appeared to be safe and generally well tolerated. Higher doses of liraglutide merit study in future clinical trials.
利拉鲁肽（NN2211）是一种长效胰高血糖素样肽-1（GLP-1）类似物，其药代动力学特征适合每日一次给药。这项多中心、双盲、平行组、双模拟研究探讨了利拉鲁肽对2型糖尿病患者体重和血糖控制影响的剂量反应关系。
纳入此前接受口服抗糖尿病药物（OAD）单药治疗（69%使用二甲双胍）且糖化血红蛋白（HbA1c）≤10%的2型糖尿病患者（体重指数27 - 42kg/m²）。经过4周二甲双胍导入期后，210名受试者（年龄27 - 73岁，60%为女性）被随机分组，分别接受每日一次利拉鲁肽（0.045 - 0.75mg）或继续使用二甲双胍1000mg每日两次，为期12周。
六个治疗组的平均基线值为：HbA1c范围为6.8%至7.5%，空腹血糖为8.06 - 9.44mmol/L（145 - 170mg/dl）。治疗12周后，六个治疗组的体重变化为 -0.05%至 -1.9%。利拉鲁肽0.045mg、0.225mg、0.45mg、0.6mg、0.75mg组以及二甲双胍组的HbA1c较基线的平均变化分别为 +1.28%、 +0.86%、 +0.22%、 +0.16%、 +0.30%和 +0.09%。在利拉鲁肽三个最高剂量水平（0.45mg、0.6mg和0.75mg）下，利拉鲁肽组与二甲双胍组的HbA1c无显著差异。利拉鲁肽最低的两个剂量（0.045mg和0.225mg）不足以维持二甲双胍所达到的空腹血糖值。未报告严重低血糖事件。接受利拉鲁肽的11名患者（6.3%）和接受二甲双胍的3名患者（8.8%）报告了恶心和/或呕吐事件。
每日一次的利拉鲁肽在改善血糖控制和体重方面与二甲双胍相当。利拉鲁肽似乎安全且耐受性良好。更高剂量的利拉鲁肽值得在未来临床试验中研究。
