Once-daily liraglutide (1.2 mg) compared with twice-daily exenatide (10 μg) in the treatment of type 2 diabetes patients: An indirect treatment comparison meta-analysis

• Published in: Journal of diabetes Vol. 8; no. 6; pp. 866 - 876
• Main Authors: Twigg, Stephen M., Daja, Mirella M., O'leary, Beth A., Adena, Michael A.
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.11.2016; John Wiley & Sons, Inc
• Subjects: 2型糖尿病; Blood Glucose - analysis; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Drug Administration Schedule; exenatide; Glycated Hemoglobin A - analysis; HbA1c; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; liraglutide; Liraglutide - administration & dosage; Liraglutide - adverse effects; Liraglutide - therapeutic use; meta-analysis; meta分析; Peptides - administration & dosage; Peptides - adverse effects; Peptides - therapeutic use; Randomized Controlled Trials as Topic; type 2 diabetes; Venoms - administration & dosage; Venoms - adverse effects; Venoms - therapeutic use; 利拉鲁肽; 艾塞那肽; liraglutide; meta分析; type 2 diabetes; 利拉鲁肽; 艾塞那肽; meta-analysis; HbA1c; 2型糖尿病; exenatide
• ISSN: 1753-0393; 1753-0407; 1753-0407
• DOI: 10.1111/1753-0407.12372

Background Glucagon‐like peptide‐1 receptor agonists provide effective hyperglycemia management in patients with type 2 diabetes. In a randomized head‐to‐head trial, liraglutide 1.8 mg q.d. led to greater reductions in HbA1c than exenatide 10 μg b.i.d. There are no direct comparisons of liraglutide 1.2 mg q.d. and exenatide b.i.d.; therefore, in the present study, an indirect comparison and meta‐analysis were undertaken. Methods A systematic literature search was performed for randomized controlled trials of liraglutide 1.2 mg q.d. or exenatide b.i.d. with HbA1c as an outcome and ≥25 subjects. Key data were extracted and analyzed. A random‐effects model was used to incorporate heterogeneity between studies. Results Three liraglutide 1.2 mg q.d. (n = 1060) and 10 exenatide b.i.d. (n = 2609) placebo‐controlled studies were identified, allowing indirect comparison with placebo as the common arm. Baseline characteristics were mean age ~55 years, disease duration ~7 years, HbA1c ~8%, and body mass index ~32 kg/m2. Compared with exenatide b.i.d., liraglutide 1.2 mg was associated with significantly greater reductions from baseline in HbA1c (–0.29%; 95% confidence interval [CI] –0.53, –0.05) and fasting plasma glucose (–0.92 mmol/L; 95% CI –1.43, –0.41), with shorter duration of nausea (3 vs 14 days; P = 0.002) and fewer withdrawals (odds ratio 0.34; 95% CI 0.22, 0.52). The incidence of adverse events (including nausea) and withdrawals because of adverse events were similar between treatments. Conclusions Liraglutide 1.2 mg provided a significantly greater reduction in HbA1c than exenatide 10 μg b.i.d. The significantly shorter duration of nausea with liraglutide than exenatide may be appreciated by patients. 摘要 背景: 胰高血糖素样肽‐1受体激动剂可以有效地治疗2型糖尿病患者的高血糖。在一项随机的头对头试验中,利拉鲁肽1.8mg每日1次与艾塞那肽10μg 每日2次相比可以更好地降低HbA1c。目前还没有利拉鲁肽1.2mg 每日1次与艾塞那肽每日2次的直接对比研究;因此,在当前的这项研究中,我们对间接对比进行了meta分析。 方法: 我们进行了系统的文献检索,入选的随机对照试验都是利拉鲁肽1.2 mg每日1次或者艾塞那肽每日2次相关的研究,要求具有HbA1c终点并且受试者≥25名。我们从中提取出关键的数据进行分析。使用随机效应模型来处理研究之间的异质性。 结果: 经过鉴定总共有3项利拉鲁肽1.2 mg每日1次(n = 1060)以及10项艾塞那肽每日2次(n = 2609)相关的安慰剂对照研究,允许将安慰剂作为普通分组进行间接对比。基线特征如下:平均年龄约为55岁,疾病病程约为7年,HbA1c约为8%,体重指数约为32 kg/m2。与艾塞那肽每日2次相比,患者使用利拉鲁肽1.2 mg每日1次治疗后HbA1c(‐0.29%;95%可信区间[CI]为‐0.53,‐0.05)以及空腹血糖(‐0.92 mmol/L;95% CI为‐1.43,‐0.41)从基线的降幅显著更大,恶心症状持续的时间更短(分别为3与14日;P = 0.002),并且停药的患者也更少(优势比为0.34;95% CI为0.22,0.52)。在两个治疗组之间不良事件(包括恶心)的发生率以及因为不良事件而导致的停药率都相类似。 结论: 与艾塞那肽10 μg每日2次相比,利拉鲁肽1.2 mg每日1次导致的HbA1c下降更显著。与艾塞那肽相比,患者可能更喜欢利拉鲁肽,因为它导致的恶心持续时间显著更短。 (a) Odds ratios for the proportion of subjects who developed treatment‐emergent nausea with liraglutide 1.2 mg q.d. versus exenatide 10 μg b.i.d. Odds ratio for liraglutide 1.2 mg q.d. add‐on compared with exenatide 10 μg b.i.d. add‐on using placebo add‐on as the common reference: 0.81 (95% confidence interval [CI] 0.41, 1.61). met, metformin; rosi, rosiglitazone; SU, sulfonylurea. (b) Mean difference between liraglutide 1.2 mg q.d. and exenatide 10 μg b.i.d. (active treatments) and placebo in the duration of nausea. *Unpaired t‐test. Mean time calculated using the trapezoidal rule.