Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark.
Diabetes Obes Metab. 2012 Aug;14(8):762-7. doi: 10.1111/j.1463-1326.2012.01603.x. Epub 2012 Apr 24.
During recent years, two strategies of incretin-based therapy [glucagon-like peptide-1 (GLP-1) receptor agonism and dipeptidyl peptidase-4 (DPP-4) inhibition] have entered the market for pharmacological management of type 2 diabetes. A main indication for this therapy is as add-on to on-going metformin therapy in subjects with type 2 diabetes who have insufficient glycaemic control with metformin alone. The aim of this study was to compare improvements in glycaemic control and changes in body weight, as well as adverse events, in comparable studies with incretin-based therapy as add-on to metformin.
Studies having a duration of 16-30 weeks were identified from PubMed.
A total of 27 study groups in 21 studies fulfilled the criteria of examining incretin-based therapy as add-on to metformin at clinically recommended doses in patients with type 2 diabetes for 16-30 weeks; 7 of these used a short-acting GLP-1 receptor agonist (exenatide BID), 7 used longer acting GLP-1 receptor agonists (liraglutide or exenatide LAR), whereas 14 studies examined DPP-4 inhibitors. In all studies, incretin-based therapy reduced HbA1c concentrations. The reduction in HbA1c was significantly greater in study groups with long-acting GLP-1 receptor agonists than with the other two groups (both p < 0.001), whereas there were no differences between exenatide BID and DPP-4 inhibitors. Across all study groups, there was a negative linear correlation between baseline HbA1c and change in HbA1c (r = -0.70; p < 0.001). Fasting glucose also fell significantly more in study groups given liraglutide or exenatide LAR than in those given exenatide BID or DPP-4 inhibitors (both p < 0.001). Furthermore, body weight was reduced by a similar extent in the two groups with GLP-1 receptor agonists and was not significantly altered in the groups with DPP-4 inhibitors. Lipids, blood pressure and heart rate were not reported consistently, which did not allow general conclusions. Adverse events were rare, apart from increased incidence of nausea and vomiting with GLP-1 receptor agonists.
Incretin-based therapy efficiently improves glycaemia when added to metformin in patients with type 2 diabetes, and within 16-30 weeks there is a more pronounced reduction in HbA1c with long-acting GLP-1 receptor agonists (liraglutide and exenatide LAR) than with exenatide BID and DPP-4 inhibitors, although the magnitude of the effect is dependent on the baseline values. Both strategies appear to be associated with a very low risk of adverse events, including hypoglycaemia. Finally, the injectable GLP-1 receptor agonists also reduce body weight (whereas the DPP-4 inhibitors are weight neutral) but are also associated with a greater incidence of gastrointestinal side effects and a tendency to increase heart rate.
近年来，两种基于肠降血糖素的治疗策略[胰高血糖素样肽-1（GLP-1）受体激动剂和二肽基肽酶-4（DPP-4）抑制剂]已进入 2 型糖尿病的药物治疗市场。这种治疗的主要适应证是在单独使用二甲双胍血糖控制不佳的 2 型糖尿病患者中，作为二甲双胍的附加治疗。本研究旨在比较在可比研究中，基于肠降血糖素的治疗作为二甲双胍的附加治疗，对血糖控制的改善和体重变化以及不良事件的影响。
从 PubMed 中确定了持续时间为 16-30 周的研究。
共有 21 项研究中的 27 个研究组符合标准，这些研究在推荐剂量下，将基于肠降血糖素的治疗作为二甲双胍的附加治疗，用于 16-30 周的 2 型糖尿病患者；其中 7 项研究使用了短效 GLP-1 受体激动剂（艾塞那肽 BID），7 项研究使用了长效 GLP-1 受体激动剂（利拉鲁肽或艾塞那肽 LAR），而 14 项研究则使用了 DPP-4 抑制剂。在所有研究中，基于肠降血糖素的治疗均降低了 HbA1c 浓度。长效 GLP-1 受体激动剂组的 HbA1c 降低幅度明显大于其他两组（均 p < 0.001），而艾塞那肽 BID 组和 DPP-4 抑制剂组之间没有差异。在所有研究组中，基线 HbA1c 与 HbA1c 变化之间呈负线性相关（r = -0.70；p < 0.001）。空腹血糖也明显降低，使用利拉鲁肽或艾塞那肽 LAR 的研究组比使用艾塞那肽 BID 或 DPP-4 抑制剂的研究组（均 p < 0.001）。此外，GLP-1 受体激动剂组的体重减轻程度相似，而 DPP-4 抑制剂组的体重无明显变化。血脂、血压和心率并未得到一致报告，因此无法得出一般性结论。不良事件很少见，除了 GLP-1 受体激动剂组恶心和呕吐的发生率增加。
在 2 型糖尿病患者中，基于肠降血糖素的治疗作为二甲双胍的附加治疗可有效改善血糖，并且在 16-30 周内，长效 GLP-1 受体激动剂（利拉鲁肽和艾塞那肽 LAR）较艾塞那肽 BID 和 DPP-4 抑制剂可更显著降低 HbA1c，尽管作用幅度取决于基线值。这两种策略似乎都具有非常低的不良事件风险，包括低血糖。最后，注射用 GLP-1 受体激动剂还可减轻体重（而 DPP-4 抑制剂对体重无影响），但也会引起更多的胃肠道副作用，并可能导致心率增加。
