Kansai Electric Power Hospital, Osaka, Japan.
Curr Med Res Opin. 2010 May;26(5):1013-22. doi: 10.1185/03007991003672551.
Liraglutide is a once-daily human glucagon-like peptide-1 (GLP-1) analogue developed for the treatment of type 2 diabetes mellitus (T2DM). In Phase 2 and Phase 3 trials, largely conducted in populations of European descent, liraglutide has been shown to lower HbA(1C), weight and systolic blood pressure with a low risk of hypoglycaemia. This Phase 3, 24-week, multi-centre, double-blind, double dummy, randomised parallel-group trial compared the efficacy and safety of liraglutide and glibenclamide monotherapy in Japanese subjects with T2DM, inadequately controlled with diet therapy or oral antidiabetic drug (OAD) monotherapy.
A total of 411 Japanese subjects were randomised 2:1 to liraglutide (n = 272) or glibenclamide (n = 139). Liraglutide was administered at a maximum planned dose of 0.9 mg once daily. Glibenclamide was administered once or twice daily at a planned maximum dose of 2.5 mg/day, before or after meals.
NCT00393718.
After 24 weeks, glycaemic control with liraglutide was non-inferior/superior to glibenclamide, with HbA(1C) at 24 weeks of 6.99% (SE +/- 0.07) with liraglutide and 7.50% (+/-0.09) with glibenclamide (difference, -0.5%; 95% CI -0.70 to 0.30; p < 0.0001). Mean fasting plasma glucose (FPG) levels at 24 weeks were significantly lower with liraglutide (7.6 mmol/l [SE +/- 0.1]) vs glibenclamide (8.3 mmol/l [+/-0.1]; difference, -0.72 mmol/l; 95% CI -1.0 to -0.4; p < 0.0001). Weight was reduced by -0.92 kg from a baseline of 65.2 kg in liraglutide-treated patients, compared with weight gain of +0.99 kg from a baseline of 64.8 kg with glibenclamide (difference, -1.91 kg; 95% CI -2.34 to -1.48; p < 0.0001). A significantly lower rate of minor hypoglycaemic episodes was achieved with liraglutide compared with glibenclamide (p < 0.0001), and no major hypoglycaemic episodes were reported in either treatment group. The most common gastrointestinal AEs were diarrhoea (liraglutide, 6.3%; glibenclamide, 3.8%) and constipation (liraglutide, 5.6%; glibenclamide, 3.8%). Nausea was infrequent (liraglutide, 4.5%; glibenclamide, 1.5%).
Liraglutide monotherapy, administered once daily for 24 weeks in Japanese subjects with T2DM, was well tolerated. Compared with glibenclamide monotherapy, liraglutide achieved superior glycaemic control and weight outcome, and a significantly lower incidence of hypoglycaemia. Future studies, comprising a greater proportion of true therapy-naïve Japanese patients, will be beneficial in order to establish the true add-on efficacy of liraglutide monotherapy in patients with T2DM.
利拉鲁肽是一种每日一次的人胰高血糖素样肽-1（GLP-1）类似物，用于治疗 2 型糖尿病（T2DM）。在 2 期和 3 期临床试验中，利拉鲁肽主要在欧洲裔人群中进行了研究，结果表明其可降低 HbA（1C）、体重和收缩压，且低血糖风险低。这项 24 周、多中心、双盲、双模拟、随机平行组 3 期临床试验比较了利拉鲁肽与格列本脲单药治疗在饮食治疗或口服降糖药（OAD）单药治疗控制不佳的日本 T2DM 患者中的疗效和安全性。
共有 411 名日本患者被随机分为 2:1 的利拉鲁肽（n = 272）或格列本脲（n = 139）组。利拉鲁肽的最大计划剂量为每天 0.9 毫克，每日一次给药。格列本脲的最大计划剂量为每天 2.5 毫克，每日一次或两次给药，饭前或饭后。
NCT00393718。
24 周后，利拉鲁肽的血糖控制与格列本脲相比具有非劣效/优效性，24 周时 HbA（1C）分别为 6.99%（SE +/- 0.07）和 7.50%（+/-0.09）（差值，-0.5%；95%CI-0.70 至 0.30；p < 0.0001）。24 周时利拉鲁肽（7.6mmol/l [SE +/- 0.1]）的空腹血浆葡萄糖（FPG）水平明显低于格列本脲（8.3mmol/l [+/-0.1]）（差值，-0.72mmol/l；95%CI-1.0 至-0.4；p < 0.0001）。与格列本脲组体重从 64.8 公斤基线增加 0.99 公斤相比，利拉鲁肽组体重从 65.2 公斤基线减轻 0.92 公斤（差值，-1.91 公斤；95%CI-2.34 至-1.48；p < 0.0001）。与格列本脲相比，利拉鲁肽组低血糖发作的发生率显著降低（p < 0.0001），两组均未报告严重低血糖发作。最常见的胃肠道不良事件是腹泻（利拉鲁肽，6.3%；格列本脲，3.8%）和便秘（利拉鲁肽，5.6%；格列本脲，3.8%）。恶心少见（利拉鲁肽，4.5%；格列本脲，1.5%）。
在日本 2 型糖尿病患者中，每日一次给予利拉鲁肽治疗 24 周，耐受性良好。与格列本脲单药治疗相比，利拉鲁肽在血糖控制和体重方面取得了更好的效果，且低血糖发生率显著降低。未来的研究，包括更多真正的初治日本患者，将有助于确定利拉鲁肽单药治疗在 2 型糖尿病患者中的真正附加疗效。
