Green Jennifer, Feinglos Mark
Duke University Medical Center, Department of Medicine, Division of Endocrinology, Durham, North Carolina 27710, USA.
Vasc Health Risk Manag. 2008;4(4):743-51. doi: 10.2147/vhrm.s3105.
Type 2 diabetes mellitus is an increasingly prevalent condition worldwide. The complications of this disease are known to significantly increase the morbidity and mortality of those affected, resulting in substantial direct and indirect costs. Although good glycemic control has been shown to reduce the incidence and progression of diabetes-related microvascular complications, blood glucose levels are not adequately controlled in most individuals with diabetes. The reasons for this are many, and include issues such as poor adherence to complex medication regimes; costs of prescribed therapies; and the failure of traditionally prescribed medications to preserve beta cell function over time. However, our armamentarium of glucose-lowering drugs has expanded recently with the development of medications that act via the incretin pathway. Sitagliptin, the first commercially available dipeptidyl peptidase-4 inhibitor, inhibits the metabolism and inactivation of the incretin hormones GLP-1 and GIP. The subsequent elevation in levels of these hormones and associated prolongation of their actions has been shown to increase insulin secretion and suppress glucagon secretion in a glucose-appropriate fashion. Sitagliptin therapy in individuals with type 2 diabetes has been found to lower significantly hemoglobin A1c (Hb1c) levels with a minimum of adverse side effects such as weight gain or hypoglycemia. Use of sitagliptin in conjunction with the insulin-sensitizing medication metformin has been shown to decrease HbAlc levels more significantly than does either drug alone. This combination of medications is generally well tolerated, with no adverse effects on weight and a very low likelihood of treatment-related hypoglycemia. Use of both drugs will positively affect many of the underlying metabolic abnormalities associated with type 2 diabetes, including the disordered secretion of insulin and glucagon as well as impaired sensitivity to insulin which are known to accompany this disease. Animal studies also suggest that dipeptidyl peptidase-4 inhibitor treatment may help to preserve beta cell mass; however, it is unclear at present whether or not this will prove to be the case in humans.
2型糖尿病在全球范围内的患病率日益上升。已知该疾病的并发症会显著增加患者的发病率和死亡率，导致大量的直接和间接成本。尽管良好的血糖控制已被证明可降低糖尿病相关微血管并发症的发生率和进展，但大多数糖尿病患者的血糖水平并未得到充分控制。原因众多，包括对复杂药物治疗方案的依从性差、处方治疗的费用以及传统处方药物无法长期维持β细胞功能等问题。然而，随着通过肠促胰岛素途径起作用的药物的开发，我们的降糖药物储备最近有所扩大。西他列汀是首个上市的二肽基肽酶-4抑制剂，可抑制肠促胰岛素激素GLP-1和GIP的代谢及失活。这些激素水平的随后升高及其作用的相关延长已被证明能以葡萄糖适宜的方式增加胰岛素分泌并抑制胰高血糖素分泌。已发现西他列汀治疗2型糖尿病患者可显著降低糖化血红蛋白（Hb1c）水平，且副作用最小，如体重增加或低血糖。与胰岛素增敏药物二甲双胍联合使用西他列汀已被证明比单独使用任何一种药物更能显著降低HbAlc水平。这种药物组合通常耐受性良好，对体重无不良影响，且治疗相关低血糖的可能性非常低。同时使用这两种药物将对与2型糖尿病相关的许多潜在代谢异常产生积极影响，包括胰岛素和胰高血糖素的分泌紊乱以及已知伴随该疾病的胰岛素敏感性受损。动物研究还表明，二肽基肽酶-4抑制剂治疗可能有助于保留β细胞数量；然而，目前尚不清楚在人类中是否也会如此。
