Ji Qiuhe
Department of Endocrinology, Xijing Hospital, The First Affiliated Hospital of the Fourth Military Medical University, Xian, People's Republic of China.
Clin Ther. 2017 Jun;39(6):1244-1264. doi: 10.1016/j.clinthera.2017.03.013. Epub 2017 May 16.
The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain. The present review discusses the place of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of obese patients with T2DM and the significance of these drugs in the prevention of future CV risk in patients with T2DM.
A literature search of PubMed and EMBASE was conducted by using the search terms T2DM, GLP-1RAs, obesity, and cardiovascular complication. Randomized controlled trials measuring the effect of GLP-1RAs versus that of placebo on CV outcomes were included in the review.
GLP-1RAs have emerged as a therapeutic alternative; these drugs exert their actions by providing glycemic control, improving insulin resistance and ö̇-cell function, and reducing weight. The risk of hypoglycemia with GLP-1RAs is minimal; however, GLP-1RAs are associated with gastrointestinal adverse events and raise concerns regarding pancreatitis. Combining GLP-1RAs with insulin analogues results in higher efficacy, a lowered insulin dose, and reduced insulin-related hypoglycemia and weight gain. Longer acting GLP-1RAs are also associated with improvement in medication adherence. Improvement in CV risk factors such as blood pressure and lipid profile further increases their usability for improving CV outcomes.
Overall, the properties of GLP-1RAs make them suitable for combination with oral antidiabetic drugs in the early stages of T2DM and with insulins in the later stages for optimizing comprehensive management of the disease.
2型糖尿病（T2DM）的进展特性要求逐步强化治疗，以维持正常血糖水平并降低心血管（CV）风险。由于肥胖是T2DM的一个突出风险因素和合并症，它会进一步提高T2DM患者的CV风险。因此，管理体重、肥胖和血糖参数对于有效管理T2DM至关重要。很少有口服抗糖尿病药物（磺脲类和噻唑烷二酮类）以及胰岛素不适用于肥胖的T2DM患者，因为这些药物会导致体重增加。本综述讨论了胰高血糖素样肽-1受体激动剂（GLP-1RAs）在肥胖T2DM患者治疗中的地位以及这些药物在预防T2DM患者未来CV风险中的意义。
通过使用搜索词T2DM、GLP-1RAs、肥胖和心血管并发症，对PubMed和EMBASE进行文献检索。本综述纳入了测量GLP-1RAs与安慰剂对CV结局影响的随机对照试验。
GLP-1RAs已成为一种治疗选择；这些药物通过控制血糖、改善胰岛素抵抗和β细胞功能以及减轻体重来发挥作用。GLP-1RAs导致低血糖的风险极小；然而，GLP-1RAs与胃肠道不良事件相关，并引发了对胰腺炎的担忧。将GLP-1RAs与胰岛素类似物联合使用可提高疗效、降低胰岛素剂量，并减少与胰岛素相关的低血糖和体重增加。长效GLP-1RAs还与药物依从性的改善有关。血压和血脂谱等CV危险因素的改善进一步增加了它们在改善CV结局方面的可用性。
总体而言，GLP-1RAs的特性使其适合在T2DM早期与口服抗糖尿病药物联合使用，在后期与胰岛素联合使用，以优化疾病的综合管理。
