Department of Medicine IV, Eberhard-Karls-University Tübingen, Otfried-Müller Strasse 10, 72076 Tübingen, Germany.
Ther Adv Endocrinol Metab. 2013 Jun;4(3):95-105. doi: 10.1177/2042018813486165.
Dipeptidyl-peptidase-IV (DPP-4) inhibitors have become an important orally active drug class for the treatment of type 2 diabetes as second-line therapy after metformin failure or as monotherapy or combination therapy with other drugs when metformin is not tolerated or contraindicated. DPP-4 inhibitors act mainly by increasing endogenous incretin hormone concentrations. They stimulate insulin secretion and inhibit glucagon secretion in a glucose-dependent manner with a significantly lower risk for hypoglycaemia than sulfonylureas. Furthermore, DPP-4 inhibitors are weight neutral. Linagliptin is a DPP-4 inhibitor that is eliminated by a hepatobiliary route, whereas the other DPP-4 inhibitors available today show a renal elimination. Therefore, it can be used in normal kidney function as well as in all stages of chronic kidney disease to stage 5 (glomerular filtration rate <15 ml/min/1.73 m(2)) without dose adjustments. Linagliptin was noninferior to metformin and sulfonylureas in clinical studies. In recent studies, it showed a superior safety profile over sulfonylurea treatment regarding hypoglycaemia and weight gain. More patients reached an HbA1c <7% without hypoglycaemia and weight gain with linagliptin compared with glimepiride. The safety profile with respect to a composite cardiovascular endpoint and stroke was also favourable for linagliptin, most likely due to a higher incidence of hypoglycaemia associated with glimepiride therapy and titration. This review gives an overview on the efficacy and safety of linagliptin in comparison with other antidiabetic drugs in type 2 diabetes patients with renal and cardiovascular risk factors as well as an outlook on the perspective for linagliptin in this patient population in the future.
二肽基肽酶-4（DPP-4）抑制剂已成为治疗 2 型糖尿病的重要口服药物类别，可作为二甲双胍治疗失败后的二线治疗药物，也可作为与其他药物联合治疗或单药治疗药物，适用于不能耐受或禁忌使用二甲双胍的患者。DPP-4 抑制剂主要通过增加内源性肠促胰岛素激素浓度发挥作用。它们以葡萄糖依赖的方式刺激胰岛素分泌并抑制胰高血糖素分泌，低血糖风险明显低于磺酰脲类药物。此外，DPP-4 抑制剂对体重无影响。利格列汀是一种通过肝胆途径消除的 DPP-4 抑制剂，而目前可用的其他 DPP-4 抑制剂则显示出肾脏消除途径。因此，它可用于正常肾功能以及慢性肾脏病的所有阶段，包括肾小球滤过率<15ml/min/1.73m²，无需调整剂量。利格列汀在临床研究中与二甲双胍和磺酰脲类药物的疗效相当。在最近的研究中，与磺酰脲类药物治疗相比，它在低血糖和体重增加方面显示出更优的安全性。与格列美脲相比，更多的患者达到了 HbA1c<7%且不发生低血糖和体重增加。与格列美脲治疗和滴定相关的低血糖发生率较高，可能是利格列汀在复合心血管终点和中风方面具有良好安全性的原因。本文综述了利格列汀在伴有肾和心血管危险因素的 2 型糖尿病患者中的疗效和安全性，并展望了未来在该患者人群中的应用前景。
