Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania Catania, Italy.
Front Endocrinol (Lausanne). 2013 Feb 26;4:16. doi: 10.3389/fendo.2013.00016. eCollection 2013.
Linagliptin, one of the five dipeptidyl peptidase-4 inhibitors available, has recently entered the market both in the US and in most European countries for treatment of type 2 diabetes mellitus. It presents a xanthine-based structure, and is characterized by unique pharmacokinetics, with non-linear profile, long terminal half-life allowing prolonged exposure to the drug. It is eliminated predominately through the intestinal tract and only minimally into urine, so that it can be administered, without any dose adjustment, in conditions of renal impairment. Linagliptin is effective in modifying all parameters of hyperglycemia either in monotherapy, or as add-on therapy, together with metformin or a sulfonylurea. It also exhibits a good tolerability profile with few side effects, absence (when used in monotherapy), or low risk (when in combination with a sulfonylurea) of hypoglycemia. More importantly it has a weight neutral effect. A comprehensive report of the literature on linagliptin is provided, paying attention in particular to preclinical studies, interactions with other drugs, safety and tolerability, and results obtained in animal models that highlight properties of linagliptin suggestive of potential additional uses. Particularly promising appear the data demonstrating a positive effect of linagliptin on metabolic dysfunction and renal and/or cardiovascular damage together with more recently reported effects of linagliptin on tissue repair and neuroprotection.
利拉利汀是 5 种二肽基肽酶-4 抑制剂之一，最近已在美国和大多数欧洲国家上市，用于治疗 2 型糖尿病。它具有黄嘌呤结构，其药代动力学特征独特，呈非线性，半衰期长，使药物的暴露时间延长。它主要通过肠道消除，仅有少量通过尿液排泄，因此在肾功能受损的情况下无需调整剂量。利拉利汀在单药治疗或与二甲双胍或磺酰脲类药物联合治疗时，均能有效改善高血糖的所有参数。它还具有良好的耐受性，副作用少（单药治疗时）或低血糖风险低（与磺酰脲类药物联合治疗时）。更重要的是，它对体重无影响。本文全面报告了利拉利汀的文献，特别关注了临床前研究、与其他药物的相互作用、安全性和耐受性，以及在动物模型中获得的结果，这些结果突出了利拉利汀的特性，提示其可能有潜在的额外用途。特别有前景的是，有数据表明利拉利汀对代谢功能障碍以及肾脏和/或心血管损伤有积极作用，以及最近报道的利拉利汀对组织修复和神经保护的作用。
