1 Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia 23298-0533, USA.
Pharmacotherapy. 2011 Sep;31(9):896-911. doi: 10.1592/phco.31.9.896.
Liraglutide is a United States Food and Drug Administration (FDA)-approved glucagon-like peptide-1 (GLP-1) analog that is 97% homologous to native human GLP-1. The additional 16-carbon fatty acid chain causes noncovalent binding to albumin, which slows absorption from the injection site and protects the molecule from degradation by the enzyme dipeptidyl peptidase-4, allowing for protraction of action. Albumin binding and an elimination half-life of 13 hours combine to allow for once-daily dosing. Liraglutide 1.2 and 1.8 mg/day given as monotherapy for up to 52 weeks produced mean reductions in hemoglobin A1c (A1C) of 0.6-1.6%; combination therapy of liraglutide with oral antidiabetic agents demonstrated mean A1C reductions up to 1.5%. The satiety effect of GLP-1 receptor agonists and documented weight loss as great as 3.38 kg in clinical trials may make liraglutide ideal for obese patients with type 2 diabetes mellitus. Like other incretin-based agents, preliminary studies suggest liraglutide may also increase β-cell mass and function. Hypoglycemia is rare with liraglutide and tends to occur when used in combination with sulfonylureas; liraglutide in combination with insulin is not yet FDA approved. The pharmacokinetic parameters of liraglutide are unaffected by age, sex, race, or ethnicity, and no special recommendations for altered dosing of liraglutide need apply to populations with hepatic or renal impairment. Results from clinical trials have not shown an increased risk of medullary thyroid cancer, pancreatitis, or poor cardiovascular outcomes with liraglutide treatment. Ongoing, long-term monitoring studies continue to evaluate the safety of liraglutide treatment in these outcomes.
利拉鲁肽是一种获得美国食品药品监督管理局（FDA）批准的胰高血糖素样肽-1（GLP-1）类似物，与天然人类 GLP-1 有 97%的同源性。额外的 16 个碳脂肪酸链导致与白蛋白的非共价结合，从而减缓从注射部位的吸收，并保护分子免受二肽基肽酶-4 酶的降解，从而延长作用时间。白蛋白结合和 13 小时的消除半衰期结合允许每日一次给药。作为单药治疗，1.2 和 1.8 mg/天的利拉鲁肽治疗长达 52 周，可使血红蛋白 A1c（A1C）平均降低 0.6-1.6%；利拉鲁肽与口服抗糖尿病药物联合治疗可使 A1C 平均降低高达 1.5%。GLP-1 受体激动剂的饱腹感效应和临床试验中高达 3.38 公斤的体重减轻可能使利拉鲁肽成为肥胖 2 型糖尿病患者的理想选择。与其他基于肠促胰岛素的药物一样，初步研究表明，利拉鲁肽还可能增加β细胞的质量和功能。利拉鲁肽很少引起低血糖，当与磺酰脲类药物联合使用时更容易发生；利拉鲁肽与胰岛素联合使用尚未获得 FDA 批准。利拉鲁肽的药代动力学参数不受年龄、性别、种族或民族的影响，对于肝功能或肾功能受损的人群，不需要特别建议调整利拉鲁肽的剂量。临床试验结果并未显示利拉鲁肽治疗与甲状腺髓样癌、胰腺炎或不良心血管结局风险增加有关。正在进行的长期监测研究继续评估利拉鲁肽治疗在这些结局中的安全性。
