Advanced Internal Medicine Group, PC, New Hyde Park, NY, USA.
Postgrad Med. 2011 Nov;123(6):189-201. doi: 10.3810/pgm.2011.11.2508.
The incretin system plays an important role in glucose homeostasis, largely through the actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Unlike GIP, the actions of GLP-1 are preserved in patients with type 2 diabetes mellitus, which has led to the development of injectable GLP-1 receptor (GLP-1R) agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1R agonists-which can be dosed to pharmacologic levels-act directly upon the GLP-1R. In contrast, DPP-4 inhibitors work indirectly by inhibiting the enzymatic inactivation of native GLP-1, resulting in a modest increase in endogenous GLP-1 levels. GLP-1R agonists generally lower the fasting and postprandial glucose levels more than DPP-4 inhibitors, resulting in a greater mean reduction in glycated hemoglobin level with GLP-1R agonists (0.4%-1.7%) compared with DPP-4 inhibitors (0.4%-1.0%). GLP-1R agonists also promote satiety and reduce total caloric intake, generally resulting in a mean weight loss of 1 to 4 kg over several months in most patients, whereas DPP-4 inhbitors are weight-neutral overall. GLP-1R agonists and DPP-4 inhibitors are generally safe and well tolerated. The glucose-dependent manner of stimulation of insulin release and inhibition of glucagon secretion by both GLP-1R agonists and DPP-4 inhibitors contribute to the low incidence of hypoglycemia. Although transient nausea occurs in 26% to 28% of patients treated with GLP-1R agonists but not DPP-4 inhibitors, this can be reduced by using a dose-escalation strategy. Other adverse events (AEs) associated with GLP-1R agonists include diarrhea, headache, and dizziness. The main AEs associated with DPP-4 inhibitors include upper respiratory tract infection, nasopharyngitis, and headache. Overall, compared with other therapies for type 2 diabetes mellitus with similar efficacy, incretin-based agents have low risk of hypoglycemia and weight gain. However, GLP-1R agonists demonstrate greater comparative efficacy and weight benefit than DPP-4 inhibitors.
肠促胰岛素系统在葡萄糖稳态中发挥着重要作用，主要通过葡萄糖依赖性胰岛素促分泌多肽（GIP）和胰高血糖素样肽-1（GLP-1）的作用。与 GIP 不同，GLP-1 的作用在 2 型糖尿病患者中得到保留，这导致了可注射 GLP-1 受体（GLP-1R）激动剂和口服二肽基肽酶-4（DPP-4）抑制剂的发展。GLP-1R 激动剂——可达到药效学水平——直接作用于 GLP-1R。相比之下，DPP-4 抑制剂通过抑制内源性 GLP-1 的酶失活而间接发挥作用，导致内源性 GLP-1 水平适度增加。GLP-1R 激动剂通常比 DPP-4 抑制剂更能降低空腹和餐后血糖水平，因此 GLP-1R 激动剂（0.4%-1.7%）比 DPP-4 抑制剂（0.4%-1.0%）更能显著降低糖化血红蛋白水平。GLP-1R 激动剂还能促进饱腹感并减少总热量摄入，通常会导致大多数患者在几个月内平均体重减轻 1 至 4 公斤，而 DPP-4 抑制剂总体上对体重无影响。GLP-1R 激动剂和 DPP-4 抑制剂通常安全且耐受良好。GLP-1R 激动剂和 DPP-4 抑制剂通过刺激胰岛素释放和抑制胰高血糖素分泌的葡萄糖依赖性方式，导致低血糖的发生率较低。虽然接受 GLP-1R 激动剂治疗的患者中有 26%-28%会出现短暂的恶心，但通过采用剂量递增策略可以减少这种情况。与 GLP-1R 激动剂相关的其他不良事件（AE）包括腹泻、头痛和头晕。与 DPP-4 抑制剂相关的主要 AE 包括上呼吸道感染、鼻咽炎和头痛。总体而言，与其他具有相似疗效的 2 型糖尿病治疗方法相比，基于肠促胰岛素的药物低血糖和体重增加的风险较低。然而，GLP-1R 激动剂比 DPP-4 抑制剂具有更好的疗效和减重效果。
