Heart of England National Health Service Foundation Trust (Teaching), University of Birmingham and Biomedical Research Unit, UK.
Adv Ther. 2011 Jun;28(6):447-59. doi: 10.1007/s12325-011-0028-y. Epub 2011 May 17.
The dipeptidyl peptidase 4 (DPP-4) inhibitors comprise a promising new class of agent for the management of type 2 diabetes. They possess a range of physiological effects associated with improved glycemic control including stimulation of glucose-dependent insulin secretion and suppression of glucagon secretion, and lower blood glucose levels through different, but potentially complementary, mechanisms to standard oral therapies. Linagliptin is the latest DPP-4 inhibitor to complete pivotal phase 3 trials. The data show that linagliptin provides significant, clinically meaningful and sustained improvements in glycemic control, with an incidence of adverse events similar to placebo and an excellent tolerability profile. In addition, linagliptin has been shown to be weight neutral and, importantly, there was no increased risk of hypoglycemia attributed to linagliptin use in monotherapy or combination therapy with metformin or pioglitazone. A unique characteristic of linagliptin that differentiates it from other members of the class is its primarily nonrenal route of excretion. The linagliptin phase 3 program included several hundred patients with type 2 diabetes and different stages of renal disease and the data suggest that the drug would not need dose adjustment, regardless of the degree of renal impairment. There is a particular need for safe and effective therapeutic agents that can be used when renal function declines. Linagliptin has recently been approved by the US Food and Drug Administration and may find a place in therapy as a treatment option for the significant number of patients in whom metformin and the other DPP-4 inhibitors are either contraindicated or require dose adjustment because of moderate to severe renal impairment.
二肽基肽酶 4（DPP-4）抑制剂是一种有前途的新型药物，可用于治疗 2 型糖尿病。它们具有一系列与改善血糖控制相关的生理作用，包括刺激葡萄糖依赖性胰岛素分泌和抑制胰高血糖素分泌，以及通过与标准口服疗法不同但可能互补的机制降低血糖水平。利拉利汀是最新完成关键 3 期临床试验的 DPP-4 抑制剂。数据表明，利拉利汀可显著改善血糖控制，具有临床意义且持续时间长，其不良反应发生率与安慰剂相似，具有良好的耐受性。此外，利拉利汀显示出中性体重作用，重要的是，与利拉利汀单药治疗或与二甲双胍或吡格列酮联合治疗相关的低血糖风险没有增加。利拉利汀与该类其他药物的一个独特特征是其主要的非肾脏排泄途径。利拉利汀 3 期计划纳入了数百名患有 2 型糖尿病和不同阶段肾脏疾病的患者，数据表明，无论肾功能损害程度如何，该药物都不需要调整剂量。当肾功能下降时，特别需要安全有效的治疗药物。利拉利汀最近已获得美国食品和药物管理局的批准，可能会成为治疗因中度至重度肾功能损害而禁忌使用二甲双胍和其他 DPP-4 抑制剂或需要调整剂量的大量患者的治疗选择之一。
