Kuritzky Louis, Umpierrez Guillermo, Ekoé Jean Marie, Mancillas-Adame Leonardo, Landó Laura Fernández
Department of Community Health and Family Medicine, University of Florida, Gainesville, FL.
Postgrad Med. 2014 Oct;126(6):60-72. doi: 10.3810/pgm.2014.10.2821.
Type 2 diabetes (T2D) is an increasingly common endocrine disorder that is characterized by chronic hyperglycemia and tissue compartment abnormalities, including macrovascular and microvascular complications. More than 90% of patients with T2D will be diagnosed and treated in the primary care setting. One of the relatively recent additions to the increasing array of approved antidiabetic medications is the glucagon-like peptide-1 receptor agonist class. Mechanisms of action for glucagon-like peptide-1 receptor agonists include: 1) stimulation of insulin secretion through β-cells, though only when glucose levels are elevated (hence, minimizing risk for hypoglycemia); 2) blunting of glucagon secretion; 3) increased satiety; and 4) decreased rate of release of gastric contents into the small intestine, thereby reducing glycemic load. Recent T2D treatment guidelines encourage individualization of therapy. Many patients still do not achieve optimal glycemic control. Therefore, other treatment options are important.
A literature search was performed using PubMed and MEDSCAPE to retrieve abstracts and articles pertinent to topics discussed in this review. Original research articles, reviews, and clinical trial manuscripts were identified based on relevance. Only English language articles were considered. Results In 3 phase 3 registration trials in patients with T2D, once-weekly dulaglutide demonstrated superior efficacy at the primary endpoint to metformin as monotherapy, to sitagliptin as add-on to metformin, and to exenatide twice daily as add-on to metformin and pioglitazone. The safety profile of dulaglutide in these trials is similar to currently available glucagon-like peptide-1 receptor agonists, characterized predominantly by gastrointestinal symptoms (ie, nausea, vomiting, and diarrhea). Based on these results, once-weekly dulaglutide should be a relevant additional treatment option for the management of T2D.
2型糖尿病（T2D）是一种日益常见的内分泌疾病，其特征为慢性高血糖和组织腔室异常，包括大血管和微血管并发症。超过90%的T2D患者将在初级保健机构接受诊断和治疗。在越来越多获批的抗糖尿病药物中，胰高血糖素样肽-1受体激动剂类药物是相对较新的一种。胰高血糖素样肽-1受体激动剂的作用机制包括：1）通过β细胞刺激胰岛素分泌，但仅在血糖水平升高时（因此，将低血糖风险降至最低）；2）抑制胰高血糖素分泌；3）增加饱腹感；4）降低胃内容物排入小肠的速率，从而降低血糖负荷。近期的T2D治疗指南鼓励治疗个体化。许多患者仍未实现最佳血糖控制。因此，其他治疗选择很重要。
使用PubMed和MEDSCAPE进行文献检索，以获取与本综述中讨论的主题相关的摘要和文章。根据相关性确定原始研究文章、综述和临床试验手稿。仅考虑英文文章。结果 在3项针对T2D患者的3期注册试验中，每周一次的度拉鲁肽在主要终点显示出优于单药治疗的二甲双胍、作为二甲双胍附加治疗的西他列汀以及作为二甲双胍和吡格列酮附加治疗的每日两次艾塞那肽的疗效。度拉鲁肽在这些试验中的安全性与目前可用的胰高血糖素样肽-1受体激动剂相似，主要特征为胃肠道症状（即恶心、呕吐和腹泻）。基于这些结果，每周一次的度拉鲁肽应是T2D管理的一种相关附加治疗选择。
