University of North Carolina School of Medicine, Medicine/Endocrinology, Chapel Hill, NC, USA.
Diabetes Obes Metab. 2015 Feb;17(2):145-51. doi: 10.1111/dom.12402. Epub 2014 Nov 9.
The recent type 2 diabetes American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) position statement suggested insulin is the most effective glucose-lowering therapy, especially when glycated haemoglobin (HbA1c) is very high. However, randomized studies comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once-weekly [OW; DURATION-3 (Diabetes therapy Utilization: Researching changes in A1c, weight, and other factors Through Intervention with exenatide ONce-Weekly)] and liraglutide once-daily [OD; LEAD-5 (Liraglutide Effect and Action in Diabetes)] with insulin glargine documented greater HbA1c reduction with GLP-1RAs, from baseline HbA1c ∼8.3% (67 mmol/mol). This post hoc analysis of DURATION-3 and LEAD-5 examined changes in HbA1c, fasting glucose and weight with exenatide OW or liraglutide and glargine, by baseline HbA1c quartile.
Descriptive statistics were provided for change in HbA1c, fasting glucose, weight, and insulin dose, and subjects (%) achieving HbA1c <7.0%, by baseline HbA1c quartile. Inferential statistical analysis on the effect of baseline HbA1c quartile was performed for change in HbA1c. An analysis of covariance (ANCOVA) model was used to evaluate similarity in change in HbA1c across HbA1c quartiles.
At 26 weeks, in both studies, HbA1c reduction, and proportion of subjects reaching HbA1c <7.0%, were similar or numerically greater with the GLP-1RAs than glargine for all baseline HbA1c quartiles. Fasting glucose reduction was similar or numerically greater with glargine. Weight decreased with both GLP-1RAs across all quartiles; subjects taking glargine gained weight, more at higher baseline HbA1c. Adverse events were uncommon although gastrointestinal events occurred more frequently with GLP-1RAs.
HbA1c reduction with the GLP-1RAs appears at least equivalent to that with basal insulin, irrespective of baseline HbA1c. This suggests that liraglutide and exenatide OW may be appropriate alternatives to basal insulin in type 2 diabetes, including when baseline HbA1c is very high (≥9.0%).
最近的 2 型糖尿病美国糖尿病协会/欧洲糖尿病研究协会（ADA/EASD）立场声明表明，胰岛素是最有效的降血糖治疗药物，尤其是当糖化血红蛋白（HbA1c）非常高时。然而，比较胰高血糖素样肽-1 受体激动剂（GLP-1RAs）艾塞那肽每周一次[OW；DURATION-3（糖尿病治疗利用：通过每周一次的 exenatide 干预研究 A1c、体重和其他因素的变化）]和利拉鲁肽每日一次[OD；LEAD-5（利拉鲁肽对糖尿病的作用和影响）]与甘精胰岛素的随机对照研究表明，GLP-1RAs 可使基线 HbA1c 约 8.3%（67mmol/mol）的患者 HbA1c 降低更多。这项 DURATION-3 和 LEAD-5 的事后分析根据基线 HbA1c 四分位数检查了艾塞那肽 OW 或利拉鲁肽和甘精胰岛素治疗时 HbA1c、空腹血糖和体重的变化。
提供了 HbA1c、空腹血糖、体重和胰岛素剂量变化的描述性统计数据，并按基线 HbA1c 四分位数提供了达到 HbA1c<7.0%的受试者（%）。对基线 HbA1c 四分位数的影响进行了 HbA1c 变化的推断性统计分析。使用协方差分析（ANCOVA）模型评估了 HbA1c 四分位数之间 HbA1c 变化的相似性。
在 26 周时，在这两项研究中，对于所有基线 HbA1c 四分位数，GLP-1RAs 与甘精胰岛素相比，HbA1c 降低的幅度更大，达到 HbA1c<7.0%的患者比例更高。空腹血糖降低与甘精胰岛素相似或更大。两种 GLP-1RAs 均可降低体重，在所有四分位数中；服用甘精胰岛素的患者体重增加，在基线 HbA1c 较高时增加更多。不良事件并不常见，但 GLP-1RAs 更常发生胃肠道事件。
GLP-1RAs 降低 HbA1c 的效果至少与基础胰岛素相当，而与基线 HbA1c 无关。这表明，利拉鲁肽和艾塞那肽 OW 可能是 2 型糖尿病患者的基础胰岛素的合适替代药物，包括基线 HbA1c 非常高（≥9.0%）时。
