Diabetes Centre, VU University Medical Centre, Amsterdam, Netherlands.
Lancet. 2010 Jun 26;375(9733):2234-43. doi: 10.1016/S0140-6736(10)60406-0.
Diabetes treatments are needed that are convenient, provide effective glycaemic control, and do not cause weight gain. We aimed to test the hypothesis that improvement in haemoglobin A(1c) (HbA(1c)) achieved with once weekly exenatide was superior to that achieved with insulin glargine titrated to glucose targets.
In this 26-week, open-label, randomised, parallel study, we compared exenatide with insulin glargine in adults with type 2 diabetes who had suboptimum glycaemic control despite use of maximum tolerated doses of blood-glucose-lowering drugs for 3 months or longer. Patients were randomly assigned to add exenatide (2 mg, once-a-week injection) or insulin glargine (once-daily injection, starting dose 10 IU, target glucose range 4.0-5.5 mmol/L) to their blood-glucose-lowering regimens. Randomisation was with a one-to-one allocation and block size four, stratified according to country and concomitant treatment (70% metformin only; 30% metformin plus sulphonylurea). Participants and clinical investigators were not masked to assignment, but investigators analysing data were. The primary endpoint was change in HbA(1c) from baseline, and analysis of this outcome was by modified intention to treat for all patients who received at least one dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT00641056.
456 patients were randomly allocated to treatment and were included in the modified intention-to-treat analysis (233 exenatide, 223 insulin glargine). Participants who received at least one dose of study drug and for whom baseline and at least one postbaseline measurement of HbA(1c) were available were included in the primary efficacy analysis. Change in HbA(1c) at 26 weeks was greater in patients taking exenatide (n=228; -1.5%, SE 0.05) than in those taking insulin glargine (n=220; -1.3%, 0.06; treatment difference -0.16%, 0.07, 95% CI -0.29 to -0.03). 12 (5%) of 233 patients allocated to exenatide and two (1%) of 223 taking insulin glargine discontinued participation because of adverse events (p=0.012). A planned extension period (up to 2.5 years' duration) is in progress.
Once weekly exenatide is an important therapeutic option for patients for whom risk of hypoglycaemia, weight loss, and convenience are particular concerns.
Amylin Pharmaceuticals; Eli Lilly and Company.
需要方便、有效控制血糖且不引起体重增加的糖尿病治疗方法。我们旨在检验每周一次给予艾塞那肽可改善糖化血红蛋白（HbA1c）的假设，这种改善优于根据血糖目标滴定至葡萄糖的甘精胰岛素。
在这项 26 周、开放标签、随机、平行研究中，我们比较了每周一次给予艾塞那肽与每日一次给予甘精胰岛素在接受最大耐受剂量降糖药物治疗 3 个月或更长时间后血糖控制仍不理想的 2 型糖尿病患者中的疗效。患者被随机分配至添加艾塞那肽（2 mg，每周一次注射）或甘精胰岛素（起始剂量 10 IU，目标血糖范围 4.0-5.5 mmol/L，每日一次注射）至其降糖方案中。随机分配采用 1:1 分配和 4 个区组，按国家和伴随治疗分层（仅 70%使用二甲双胍；30%使用二甲双胍加磺脲类药物）。患者和临床研究者对分配方案不设盲，但分析数据的研究者设盲。主要终点为从基线起 HbA1c 的变化，所有接受至少一剂研究药物的患者均进行改良意向治疗分析。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00641056。
456 名患者被随机分配至治疗组并纳入改良意向治疗分析（艾塞那肽组 233 名，甘精胰岛素组 223 名）。至少接受一剂研究药物且有基线和至少一次基线后 HbA1c 测量值的患者纳入主要疗效分析。接受艾塞那肽治疗的患者（n=228）26 周时 HbA1c 的变化大于接受甘精胰岛素治疗的患者（n=220；-1.3%，0.06；治疗差异-0.16%，0.07，95%CI-0.29 至 -0.03）。233 名被分配至艾塞那肽组的患者中有 12 名（5%）和 223 名接受甘精胰岛素治疗的患者中有 2 名（1%）因不良事件而退出研究（p=0.012）。目前正在进行一项为期长达 2.5 年的延长研究。
每周一次给予艾塞那肽是一种重要的治疗选择，适用于对低血糖、体重减轻和方便性特别关注的患者。
艾塞那肽制药公司；礼来公司。
