Yokoyama Hiroki, Hirao Koichi, Yamaguchi Kohei, Oishi Mariko, Lee Gendai, Yagi Noriharu, Takamura Hiroshi, Kashiwagi Atsunori
Jiyugaoka Medical Clinic, Internal Medicine, Obihiro, Japan.
HEC Science Clinic, Yokohama, Japan.
Jpn Clin Med. 2014 Sep 17;5:33-41. doi: 10.4137/JCM.S16585. eCollection 2014.
Liraglutide (glucagon-like peptide-1 [GLP-1] receptor agonist) and sitagliptin (dipeptidyl peptidase-4 inhibitor) are approved in Japan for treating type 2 diabetes mellitus (T2DM). We compared the efficacy and safety of adding liraglutide or sitagliptin to a sulfonylurea in Japanese T2DM patients.
Patients aged 18 to <80 years with hemoglobin A1c (HbA1c; National Glycohemoglobin Standardization Program [NGSP]) of 6.9-9.4%, body mass index ≤35 kg/m(2), and treatment with a sulfonylurea and/or one or two non-sulfonylurea oral antidiabetic drugs for greater than or equal to eight weeks before enrollment were eligible. Patients were randomized in an open-label manner to either 0.9 mg/day liraglutide (n = 50) or 50-100 mg/day sitagliptin (n = 49) and were treated for 24 weeks. Non-sulfonylureas were discontinued before randomization. Patients using other oral antidiabetic drugs started sulfonylurea treatment. The primary endpoint was the change in HbA1c from baseline to Week 24.
HbA1c decreased in both groups, and the reduction was significantly greater throughout in the liraglutide group except for Week 24 (0.59 ± 0.80 vs. 0.24 ± 0.94%; P = 0.0525). Fasting plasma glucose (FPG) decreased significantly in the liraglutide group compared with the sitagliptin group (-21.15 ± 31.22 vs. +0.46 ± 39.39 mg/dL; P = 0.0014). Homeostasis model assessment of β cell function and C-peptide increased significantly in the liraglutide group but not in the sitagliptin group. Hypoglycemic symptoms and adverse events occurred in four and nine patients, respectively, in the liraglutide group, and in two and five patients, respectively, in the sitagliptin group.
Treatment with liraglutide or sitagliptin together with a sulfonylurea improved HbA1c in Japanese T2DM patients in primary care. Both drugs were associated with low rates of adverse events and hypoglycemia. The improvement in β cell function probably contributed to the improvement in glycemic control in the liraglutide group.
利拉鲁肽（胰高血糖素样肽-1[GLP-1]受体激动剂）和西格列汀（二肽基肽酶-4抑制剂）在日本被批准用于治疗2型糖尿病（T2DM）。我们比较了在日本T2DM患者中，将利拉鲁肽或西格列汀添加到磺脲类药物中的疗效和安全性。
年龄在18至<80岁之间，糖化血红蛋白（HbA1c；采用国家糖化血红蛋白标准化计划[NGSP]测定）为6.9 - 9.4%，体重指数≤35 kg/m²，且在入组前接受磺脲类药物和/或一种或两种非磺脲类口服降糖药物治疗≥8周的患者符合条件。患者以开放标签的方式随机分为每日0.9 mg利拉鲁肽组（n = 50）或每日50 - 100 mg西格列汀组（n = 49），并接受24周的治疗。非磺脲类药物在随机分组前停用。使用其他口服降糖药物的患者开始接受磺脲类药物治疗。主要终点是从基线到第24周HbA1c的变化。
两组的HbA1c均下降，除第24周外，利拉鲁肽组在整个研究过程中的下降幅度均显著更大（0.59±0.80 vs. 0.24±0.94%；P = 0.0525）。与西格列汀组相比，利拉鲁肽组的空腹血糖（FPG）显著下降（-21.15±31.22 vs. +0.46±39.39 mg/dL；P = 0.0014）。利拉鲁肽组的β细胞功能稳态模型评估和C肽显著增加，而西格列汀组未增加。利拉鲁肽组分别有4例和9例患者出现低血糖症状和不良事件，西格列汀组分别有2例和5例患者出现。
在基层医疗中，利拉鲁肽或西格列汀与磺脲类药物联合治疗可改善日本T2DM患者的HbA1c。两种药物的不良事件和低血糖发生率均较低。β细胞功能的改善可能有助于利拉鲁肽组血糖控制的改善。
