Diabetes and Endocrine Division, Department of Medicine, Kawasaki Medical School, Okayama 701-0192, Japan.
Diabetes Obes Metab. 2010 Apr;12(4):341-7. doi: 10.1111/j.1463-1326.2009.01194.x.
Sulphonylureas (SUs) are often used as first-line treatments for type 2 diabetes in Japan, hence it is important to study new antidiabetic drugs in combination with SUs in Japanese patients.
The efficacy and safety of the once-daily human glucagon-like peptide-1 (GLP-1) analogue liraglutide were compared in 264 Japanese subjects [mean body mass index (BMI) 24.9 kg/m(2); mean glycated haemoglobin (HBA1c) 8.4%] randomized and exposed to receive liraglutide 0.6 mg/day (n = 88), 0.9 mg/day (n = 88) or placebo (n = 88) each added to SU monotherapy (glibenclamide, glicazide or glimeprimide) in a 24-week, double-blind, parallel-group trial.
The mean change in HBA1c from baseline to week 24 (LOCF) was -1.56 (s.d. 0.84) and -1.46 (s.d. 0.95) with liraglutide 0.9 and 0.6 mg respectively, and -0.40 (s.d. 0.93) with placebo. HBA1c decreased in the placebo group from 8.45 to 8.06%, while liraglutide reduced HBA1c from 8.60 to 7.14%, and from 8.23 to 6.67% at the 0.6 and 0.9 mg doses respectively. Mean HBA1c at week 24 of the two liraglutide groups were significantly lower than the placebo group (p < 0.0001 for both). More subjects reached HBA1c < 7.0% with liraglutide (0.6 mg: 46.5%; 0.9 mg: 71.3%) vs. placebo (14.8%). Fasting plasma glucose (FPG) levels were significantly improved with liraglutide (difference -1.47 mmol/l and -1.80 mmol/l with 0.6 and 0.9 mg vs. placebo; p < 0.0001). Overall safety was similar between treatments: no major hypoglycaemic episodes were reported, while 84/77/38 minor hypoglycaemic episodes occurred in the 0.6 mg/0.9 mg and placebo treatment groups (all in combination with SU), reflecting lower ambient glucose levels. No relevant change in mean body weight occurred in subjects receiving liraglutide (0.6 mg: 0.06 kg; 0.9 mg: -0.37 kg), while mean body weight decreased in subjects receiving placebo (-1.12 kg).
The addition of liraglutide to SU treatment for 24 weeks dose-dependently improved glycaemic control vs. SU monotherapy, without causing major hypoglycaemia or weight gain or loss.
磺酰脲类药物（SUs）通常被用作日本 2 型糖尿病的一线治疗药物，因此研究新型抗糖尿病药物与 SUs 联合用于日本患者非常重要。
在一项 264 例日本受试者（平均体重指数[BMI] 24.9kg/m2；平均糖化血红蛋白[HbA1c]8.4%）的随机、双盲、平行分组试验中，比较了每日一次的人胰高血糖素样肽-1（GLP-1）类似物利拉鲁肽在添加 SU 单药治疗（格列本脲、格列齐特或格列美脲）时的疗效和安全性。
根据末次访视（LOCf），HbA1c 从基线到 24 周的平均变化分别为利拉鲁肽 0.9mg 组和 0.6mg 组的-1.56（标准差[SD]0.84）和-1.46（SD0.95），安慰剂组为-0.40（SD0.93）。安慰剂组的 HbA1c 从 8.45%降至 8.06%，而利拉鲁肽组分别从 8.60%降至 7.14%和从 8.23%降至 6.67%。两个利拉鲁肽组的平均 HbA1c 在 24 周时均显著低于安慰剂组（均<0.0001）。与安慰剂组（14.8%）相比，更多的受试者达到了 HbA1c<7.0%的目标（利拉鲁肽 0.6mg 组：46.5%；利拉鲁肽 0.9mg 组：71.3%）。利拉鲁肽治疗组的空腹血糖（FPG）水平显著改善（利拉鲁肽 0.6mg 组和 0.9mg 组与安慰剂组相比分别为-1.47mmol/l 和-1.80mmol/l；均<0.0001）。与治疗相关的总体安全性相似：未报告严重低血糖事件，而利拉鲁肽治疗组（均与 SU 联合使用）发生 84/77/38 次轻微低血糖事件，安慰剂组发生 38 次（所有均与 SU 联合使用），这反映了更低的环境血糖水平。接受利拉鲁肽治疗的受试者体重无明显变化（利拉鲁肽 0.6mg 组：0.06kg；利拉鲁肽 0.9mg 组：-0.37kg），而接受安慰剂治疗的受试者体重减轻（-1.12kg）。
利拉鲁肽联合 SU 治疗 24 周可显著改善血糖控制，优于 SU 单药治疗，且不会导致严重低血糖或体重增加或减轻。
