Mikhail Nasser
Endocrinology Division, Department of Medicine, Olive-View-UCLA Medical Center, 14445 Olive View Drive, Sylmar, CA 91342, USA.
Expert Opin Investig Drugs. 2008 Jun;17(6):845-53. doi: 10.1517/13543784.17.6.845.
Exenatide is an incretin mimetic, while sitagliptin and vildagliptin are incretin enhancers used as adjunctive therapy in patients with type 2 diabetes failing oral agents. Sitagliptin and vildagliptin can also be used as monotherapy in patients with type 2 diabetes uncontrolled by diet.
To provide a critical review of clinical trials of exenatide, sitagliptin and vildagliptin.
Review of Phase III clinical trials based on Medline search published up to April 2008.
The use of exenatide is associated with reduction in average hemoglobin A1c (HbA1c) levels of approximately 0.8% compared with baseline. The corresponding reduction with either sitagliptin or vildagliptin is 0.7%. The actions of incretin-based drugs predominantly target postprandial hyperglycemia. Treatment-related hypoglycemia is generally mild, and mainly occurs when used with sulfonylureas (SUs). Exenatide treatment leads to a mild weight loss of around 2 kg after 30 weeks, whereas sitagliptin and vildagliptin have generally neutral effect on weight. Sitagliptin and vildagliptin are well tolerated in trials lasting up to 52 weeks. Meanwhile, 5 - 10% of patients cannot tolerate exenatide due to adverse effects, mainly nausea and vomiting. The three drugs are limited by the lack of long-term safety and efficacy data, as well as by their high cost.
Exenatide, sitagliptin and vildagliptin are useful add-on therapy for type 2 diabetes that is suboptimally controlled on oral agents, particularly when there is concern about weight gain and hypoglycemia, or when postprandial hyperglycemia is the major cause of inadequate glycemic control. Sitagliptin and vildagliptin may be used as monotherapy in patients who cannot tolerate metformin or SU, and sitagliptin may be used as alternative to metformin in renal insufficiency.
艾塞那肽是一种肠促胰岛素类似物，而西格列汀和维格列汀是肠促胰岛素增强剂，用于口服药物治疗失败的2型糖尿病患者的辅助治疗。西格列汀和维格列汀也可用于饮食控制不佳的2型糖尿病患者的单药治疗。
对艾塞那肽、西格列汀和维格列汀的临床试验进行批判性综述。
基于截至2008年4月发表的Medline搜索结果，对III期临床试验进行综述。
与基线相比，使用艾塞那肽可使平均糖化血红蛋白（HbA1c）水平降低约0.8%。西格列汀或维格列汀的相应降低幅度为0.7%。基于肠促胰岛素的药物作用主要针对餐后高血糖。与治疗相关的低血糖一般较轻，主要发生在与磺脲类药物（SUs）合用时。艾塞那肽治疗30周后导致体重轻度减轻约2kg，而西格列汀和维格列汀对体重一般无影响。在长达52周的试验中，西格列汀和维格列汀耐受性良好。同时，5% - 10%的患者因不良反应（主要是恶心和呕吐）无法耐受艾塞那肽。这三种药物因缺乏长期安全性和有效性数据以及成本高昂而受到限制。
艾塞那肽、西格列汀和维格列汀是口服药物控制不佳的2型糖尿病的有用附加治疗药物，特别是当担心体重增加和低血糖，或餐后高血糖是血糖控制不佳的主要原因时。西格列汀和维格列汀可用于不能耐受二甲双胍或SUs的患者的单药治疗，西格列汀可用于肾功能不全患者替代二甲双胍。
