Vilsbøll T, Brock B, Perrild H, Levin K, Lervang H-H, Kølendorf K, Krarup T, Schmitz O, Zdravkovic M, Le-Thi T, Madsbad S
Department of Internal Medicine F, Gentofte Hospital, Gentofte, Denmark.
Diabet Med. 2008 Feb;25(2):152-6. doi: 10.1111/j.1464-5491.2007.02333.x. Epub 2008 Jan 14.
To assess the effect of liraglutide, a once-daily human glucagon-like peptide-1 analogue on pancreatic B-cell function. methods: Patients with Type 2 diabetes (n = 39) were randomized to treatment with 0.65, 1.25 or 1.9 mg/day liraglutide or placebo for 14 weeks. First- and second-phase insulin release were measured by means of the insulin-modified frequently sampled intravenous glucose tolerance test. Arginine-stimulated insulin secretion was measured during a hyperglycaemic clamp (20 mmol/l). Glucose effectiveness and insulin sensitivity were estimated by means of the insulin-modified frequently sampled intravenous glucose tolerance test.
The two highest doses of liraglutide (1.25 and 1.9 mg/day) significantly increased first-phase insulin secretion by 118 and 103%, respectively (P < 0.05). Second-phase insulin secretion was significantly increased only in the 1.25 mg/day group vs. placebo. Arginine-stimulated insulin secretion increased significantly at the two highest dose levels vs. placebo by 114 and 94%, respectively (P < 0.05). There was no significant treatment effect on glucose effectiveness or insulin sensitivity.
Fourteen weeks of treatment with liraglutide showed improvements in first- and second-phase insulin secretion, together with improvements in arginine-stimulated insulin secretion during hyperglycaemia.
评估每日一次的人胰高血糖素样肽-1类似物利拉鲁肽对胰腺β细胞功能的影响。方法:将39例2型糖尿病患者随机分为三组,分别接受0.65毫克/天、1.25毫克/天或1.9毫克/天的利拉鲁肽治疗或安慰剂治疗,为期14周。通过胰岛素改良的频繁采样静脉葡萄糖耐量试验测量第一相和第二相胰岛素释放。在高血糖钳夹(20毫摩尔/升)期间测量精氨酸刺激的胰岛素分泌。通过胰岛素改良的频繁采样静脉葡萄糖耐量试验评估葡萄糖效能和胰岛素敏感性。
利拉鲁肽的两个最高剂量组(1.25毫克/天和1.9毫克/天)分别使第一相胰岛素分泌显著增加118%和103%(P<0.05)。仅1.25毫克/天的利拉鲁肽组与安慰剂组相比,第二相胰岛素分泌显著增加。与安慰剂相比,两个最高剂量水平的精氨酸刺激的胰岛素分泌分别显著增加114%和94%(P<0.05)。对葡萄糖效能或胰岛素敏感性没有显著的治疗效果。
利拉鲁肽治疗14周显示第一相和第二相胰岛素分泌有所改善,同时高血糖期间精氨酸刺激的胰岛素分泌也有所改善。