Diabetes Care & Research Centre, Patna, India.
Diabetes Metab Res Rev. 2012 Dec;28 Suppl 2:21-5. doi: 10.1002/dmrr.2350.
Following diagnosis, type 2 diabetic subjects are invariably treated with life style modifications and metformin. However, majority of these subjects require addition of another therapeutic agent singly or in combination; with or without insulin within few months to few years. For several decades, sulphonylureas and insulin have been the second line agent of choice. Clinical practice guidelines also suggest a similar approach. Subsequently thiazolidinediones, alpha glucose inhibitors and other agents were added to therapeutic armamentarium. Unfortunately, none of these treatment options could address the issue of progressive decline in beta cell function. Furthermore, they are responsible for unacceptable incidence of hypoglycaemia, weight gain and other side effects related to individual agents. Type 2 diabetic subjects have great propensity to develop cardiovascular complications. Sulphonylureas, insulin and thiazolidinediones have all been associated with adverse cardiovascular outcomes in differing magnitude. It has been made mandatory by regulatory agencies to ensure cardiovascular safety of any new anti-diabetic agent. Glucagon Like Peptide-1(GLP-1)-based therapies have been able to address several of these issues. Incretin mimetics and Di Peptidyl Dipeptidase IV (DPP-IV) inhibitors cause glucose-dependent insulin secretion and glucagon suppression from beta and alpha cells of the pancreas respectively. They owe this property to their binding with G-Protein-coupled receptors leading to an increased amount of c-AMP. They do not cause beta cell exhaustion. On the contrary such agents prevent beta cell apoptosis. Clinical trials have established the superiority of incretin mimetics particularly liraglutide against comparators including glimepiride, rosiglitazone and insulin Glargine in terms of efficacy. Furthermore, they have shown evidence towards beta cell protection, significant weight loss, minimal hypoglycaemia and favourable impact on surrogate markers of cardiovascular outcomes. DPP-IV inhibitors have limited ability to achieve glycaemic targets. However, they are weight neutral, cause minimal hypoglycaemia and have some beneficial effect on beta cell function. Finally, they are very well tolerated.
确诊后，2 型糖尿病患者通常采用生活方式改变和二甲双胍治疗。然而，这些患者中的大多数需要在数月至数年内单独或联合使用另一种治疗药物，包括磺酰脲类药物和胰岛素。几十年来，磺酰脲类药物和胰岛素一直是二线治疗药物。临床实践指南也建议采用类似的方法。随后，噻唑烷二酮类药物、α-葡萄糖苷酶抑制剂和其他药物被添加到治疗方案中。不幸的是，这些治疗选择都无法解决β细胞功能逐渐下降的问题。此外，它们还会导致无法接受的低血糖、体重增加和与个体药物相关的其他副作用。2 型糖尿病患者极易发生心血管并发症。磺酰脲类药物、胰岛素和噻唑烷二酮类药物都与不同程度的不良心血管结局有关。监管机构已经强制要求确保任何新的抗糖尿病药物的心血管安全性。胰高血糖素样肽-1（GLP-1）类药物治疗已经能够解决其中的一些问题。肠促胰岛素类似物和二肽基肽酶-4（DPP-4）抑制剂分别通过与胰腺β和α细胞上的 G 蛋白偶联受体结合，引起葡萄糖依赖性胰岛素分泌和胰高血糖素抑制。它们具有这种特性是因为它们与 G 蛋白偶联受体结合，导致 c-AMP 量增加。它们不会导致β细胞衰竭。相反，这些药物可以防止β细胞凋亡。临床试验已经证明了肠促胰岛素类似物（特别是利拉鲁肽）在疗效方面优于对照组，包括格列美脲、罗格列酮和甘精胰岛素。此外，它们还显示出对β细胞保护、显著体重减轻、低血糖发生率低以及对心血管结局替代标志物的有利影响。DPP-4 抑制剂在实现血糖目标方面的能力有限。然而，它们对体重没有影响，低血糖发生率低，对β细胞功能有一定的有益影响。最后，它们的耐受性非常好。
