Endocrinology, Diabetes, and Metabolism, MedStar Health Research Institute, Washington, DC 20003, USA.
Diabetes Metab Res Rev. 2011 Sep;27(6):528-42. doi: 10.1002/dmrr.1202.
Although several classes of pharmacotherapy are available for type 2 diabetes, glycaemic control is often hampered by medication-related adverse effects and contraindications such as renal impairment. Glucagon-like peptide-1 (GLP-1) receptor agonists provide a new pharmacotherapeutic option based on the multiple glucose-lowering effects of the human hormone GLP-1. This mechanism of action not only provides therapeutic efficacy but also suggests that GLP-1 receptor agonists have distinct safety and tolerability concerns compared with other diabetes therapies. Stimulation of pancreatic insulin secretion by GLP-1 receptor agonists is glucose dependent, conferring a lesser risk of hypoglycaemia than that seen with sulfonylureas. Individual GLP-1 receptor agonists differ in their metabolism and excretion profiles, affecting the choice of agent for patients with renal impairment. As with other protein-based therapies, GLP-1 receptor agonists may induce the formation of antibodies that may attenuate therapeutic efficacy and affect safety. Conclusions on cardiovascular safety must await outcomes studies, but at present no signal of harm has been reported, and preclinical data and effects on risk markers suggest a potential for benefit. Current data on thyroid medullary cancer in humans and pancreatic malignancy in rodents do not suggest that there is any reason to restrict the clinical use of GLP-1 analogues in most people with diabetes. It is currently difficult to ascertain the possible contributory role of GLP-1 receptor agonists in increasing the risk of pancreatitis, and vigilance for signs and symptoms is prudent. Primary tolerability issues include transient gastrointestinal symptoms, common with GLP-1 receptor agonists, which can be reduced through dose titration.
虽然有几类药物可用于治疗 2 型糖尿病，但由于药物相关的不良反应和禁忌证（如肾功能损害），血糖控制往往受到阻碍。胰高血糖素样肽-1（GLP-1）受体激动剂为治疗提供了新的选择，其基于人类激素 GLP-1 的多种降血糖作用。这种作用机制不仅提供了治疗效果，还表明与其他糖尿病治疗方法相比，GLP-1 受体激动剂具有明显的安全性和耐受性问题。GLP-1 受体激动剂通过刺激胰腺胰岛素分泌而起作用，这种作用与磺酰脲类药物相比低血糖风险较低。由于个体 GLP-1 受体激动剂的代谢和排泄特征不同，这会影响到肾功能损害患者的药物选择。与其他基于蛋白质的治疗方法一样，GLP-1 受体激动剂可能会诱导抗体的形成，从而可能减弱治疗效果并影响安全性。关于心血管安全性的结论必须等待结局研究，但目前尚未报告有害信号，而且临床前数据和对风险标志物的影响表明可能存在益处。目前关于人类甲状腺髓样癌和啮齿动物胰腺恶性肿瘤的数据并未表明有任何理由限制大多数糖尿病患者使用 GLP-1 类似物。目前很难确定 GLP-1 受体激动剂在增加胰腺炎风险方面的可能作用，因此谨慎观察症状和体征是明智的。主要的耐受性问题包括常见的 GLP-1 受体激动剂引起的短暂胃肠道症状，通过剂量滴定可以减少这些症状。
