Medstar Research Institute, Hyattsville, MD, USA.
Diabet Med. 2010 May;27(5):556-62. doi: 10.1111/j.1464-5491.2010.02990.x.
The study objective was to investigate the safety and tolerability of up-titration to high doses of taspoglutide, a once-weekly human glucagon-like peptide-1 analogue, in subjects with Type 2 diabetes inadequately controlled on metformin alone.
In this double-blind phase II trial, subjects were randomized to placebo or taspoglutide (20 mg; three separate groups) administered once weekly by subcutaneous injection for 4 weeks. This was followed by dose maintenance at 20 mg, or titration to 30 mg (20/30) or 40 mg (20/40) once weekly with matched placebo for an additional 4 weeks. Subjects were monitored for adverse events (AEs) throughout the study and 4-week follow-up.
One hundred and twenty-nine subjects were randomized and treated [mean age 57 years, mean baseline glycated haemoglobin (HbA(1c)), 7.9%]. The most frequently reported AEs were nausea and vomiting. The number of patients reporting gastrointestinal AEs did not increase following titration to higher doses of taspoglutide or when continuing the initial 20 mg regimen. Three subjects were withdrawn from the study as a result of gastrointestinal AEs (one before and two after titration to higher doses). Although not designed to investigate efficacy, improvement in glycaemic control was observed in all active arms of the study. The proportion of subjects achieving HbA(1c) < 7.0% after 8 weeks of treatment was 72, 53 and 70% in the 20/20-, 20/30- and 20/40-mg arms, respectively, vs. 19% for placebo.
Taspoglutide was safe, well tolerated at high doses and efficacious for lowering HbA(1c). Up-titration of dose was not associated with a worsening AE profile.
本研究旨在探讨每周一次给予高剂量塔斯格鲁肽（一种人胰高血糖素样肽-1 类似物）治疗，对单独使用二甲双胍血糖控制不佳的 2 型糖尿病患者的安全性和耐受性。
这是一项双盲的 2 期临床试验，受试者被随机分为安慰剂组或塔斯格鲁肽（20mg）组（3 个亚组），每周 1 次皮下注射给药，持续 4 周。随后，20mg 剂量维持治疗，或滴定至每周 30mg（20/30）或 40mg（20/40），同时给予匹配的安慰剂，另外 4 周。在整个研究过程中及 4 周随访期内，对受试者进行不良事件（AE）监测。
129 例受试者被随机分组并接受治疗[平均年龄 57 岁，平均基线糖化血红蛋白（HbA1c）7.9%]。最常报告的 AE 为恶心和呕吐。随着塔斯格鲁肽剂量的增加或继续使用初始 20mg 方案，报告胃肠道 AE 的患者人数并未增加。有 3 例受试者因胃肠道 AE 退出研究（1 例在剂量增加前，2 例在剂量增加后）。尽管本研究并非旨在研究疗效，但在研究的所有活性治疗组中均观察到血糖控制的改善。在治疗 8 周后，HbA1c<7.0%的受试者比例分别为 20/20mg、20/30mg 和 20/40mg 组为 72%、53%和 70%，而安慰剂组为 19%。
塔斯格鲁肽安全性良好，高剂量下耐受性良好，降 HbA1c 有效。增加剂量与不良事件谱恶化无关。
