Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Sart Tilman (B35), University of Liège, Liège, Belgium.
Diabetes Metab. 2012 Apr;38(2):89-101. doi: 10.1016/j.diabet.2011.11.001. Epub 2011 Dec 22.
Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA(1c) reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA(1c) and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-to-head trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials.
二肽基肽酶-4（DPP-4）抑制剂为 2 型糖尿病的治疗提供了新的选择。在未经药物治疗的患者中，与活性降糖对照物的直接比较表明，DPP-4 抑制剂降低糖化血红蛋白（HbA1c）的效果略低于二甲双胍（具有更好的胃肠道耐受性优势），与噻唑烷二酮（TZD；无体重增加优势）相比，降低血糖的效果相似。在接受二甲双胍治疗的患者中，与磺酰脲类药物（SU；无体重增加、低血糖发作次数明显减少且无需调整剂量的优势）和 TZD（无体重增加和整体耐受性更好的优势）相比，gliptins 与 HbA1c 的降低相似。与 SU 或 TZD 治疗的患者相比，DPP-4 抑制剂在接受 SU 或 TZD 治疗的患者中也具有临床相关的降糖作用（当二甲双胍不耐受或禁忌时可能具有潜在意义），并且当添加到二甲双胍-SU 或吡格列酮-SU 联合治疗时，具有良好的耐受性。几项临床试验还表明，DPP-4 抑制剂添加到基础胰岛素治疗时，HbA1c 持续降低，低血糖风险无增加。由于 2 型糖尿病的复杂病理生理学和降糖药物的互补作用，在未经药物治疗的患者中，DPP-4 抑制剂与二甲双胍或 glitazone 的初始联合应用可能会产生更大的疗效，与单一药物治疗相比，安全性相似。然而，与 GLP-1 受体激动剂相比，DPP-4 抑制剂降低 HbA1c 和体重的效果较差，但具有使用更方便（口服而非注射给药）和成本更低的优势。只有一项头对头试验证明 saxagliptin 与 sitagliptin 等效。显然，需要更多直接比较不同基于肠促胰岛素的治疗方法的试验。由于其药代动力学特征、药效学特性（血糖依赖性降糖作用）和良好的整体耐受性，DPP-4 抑制剂在肾功能损害和老年患者中可能具有重要作用。随着通过对照临床试验更好地定义其潜在优势和劣势，DPP-4 抑制剂在 2 型糖尿病治疗中的作用正在迅速发展。
