Incorporating incretin-based therapies into clinical practice: differences between glucagon-like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors.
Incorporating incretin-based therapies into clinical practice: differences between glucagon-like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors.
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DOI：
10.4065/mcp.2010.0469
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发表时间：
2010-12-01
影响因子：
8.9
通讯作者：
Davidson, Jaime A
中科院分区：
文献类型：
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作者：
Davidson, Jaime A
2型糖尿病（DM）是一种影响全世界儿童、青少年和成人的流行疾病。除了微血管疾病的风险外，2型糖尿病患者通常具有多种大血管疾病的风险因素;例如，约90%的2型糖尿病患者超重/肥胖。2型DM是一种复杂的疾病，涉及多种病理生理异常，包括胰岛素抵抗、肝葡萄糖产生增加和激素分泌异常，如胰岛素、胰高血糖素、胰淀素和肠促胰岛素。肠促胰岛素是一种具有多种糖调节功能的肠源性肽。肠降血糖素功能障碍可以用胰高血糖素样肽1（GLP-1）受体激动剂（例如艾塞那肽和利拉鲁肽）或二肽基肽酶4（DPP-4）抑制剂（例如西格列汀和沙格列汀）（降解GLP-1的酶）治疗。GLP-1受体激动剂和DPP-4抑制剂均能提高GLP-1活性并显著改善血糖控制。GLP-1受体激动剂在降低血糖方面更有效，并导致体重显著减轻，而DPP-4抑制剂治疗降低血糖水平的程度较低，并且体重中性。GLP-1受体激动剂治疗已证明可持久控制血糖并改善多种心血管疾病风险因素。此外，与胰岛素或磺脲类药物不同，GLP-1受体激动剂或DPP-4抑制剂治疗与严重低血糖无关。在为超重/肥胖的2型DM患者、使用其他药物时发生低血糖的患者以及难以达到血糖目标的患者选择单药治疗或联合治疗要素时，应考虑这些因素。
Type 2 diabetes mellitus (DM) is a prevalent disorder that affects children, adolescents, and adults worldwide. In addition to risks of microvascular disease, patients with type 2 DM often have multiple risk factors of macrovascular disease; for example, approximately 90% of patients with type 2 DM are overweight/obese. Type 2 DM is a complex disease that involves a variety of pathophysiologic abnormalities, including insulin resistance, increased hepatic glucose production, and abnormalities in the secretion of hormones, such as insulin, glucagon, amylin, and incretins. Incretins are gut-derived peptides with a variety of glucoregulatory functions. Incretin dysfunction can be treated with glucagon-like peptide 1 (GLP-1) receptor agonists (eg, exenatide and liraglutide) or inhibitors of dipeptidyl peptidase 4 (DPP-4) (eg, sitagliptin and saxagliptin), the enzyme that degrades GLP-1. The GLP-1 receptor agonists and DPP-4 inhibitors both elevate GLP-1 activity and substantially improve glycemic control. The GLP-1 receptor agonists are more effective in lowering blood glucose and result in substantial weight loss, whereas therapy with DPP-4 inhibitors lowers blood glucose levels to a lesser degree, and they are weight neutral. Treatment with GLP-1 receptor agonists has demonstrated durable glycemic control and improvement in multiple cardiovascular disease risk factors. In addition, unlike insulin or sulfonylureas, treatment with a GLP-1 receptor agonist or a DPP-4 inhibitor has not been associated with substantial hypoglycemia. These factors should be considered when selecting monotherapy or elements of combination therapy for patients with type 2 DM who are overweight/obese, for patients who have experienced hypoglycemia with other agents, and when achieving glycemic targets is difficult.