Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen 2630, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Cardiovasc Res. 2023 May 2;119(4):886-904. doi: 10.1093/cvr/cvac112.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been used to treat patients with type 2 diabetes since 2005 and have become popular because of the efficacy and durability in relation to glycaemic control in combination with weight loss in most patients. Today in 2022, seven GLP-1 RAs, including oral semaglutide are available for treatment of type 2 diabetes. Since the efficacy in relation to reduction of HbA1c and body weight as well as tolerability and dosing frequency vary between agents, the GLP-1 RAs cannot be considered equal. The short acting lixisenatide showed no cardiovascular benefits, while once daily liraglutide and the weekly agonists, subcutaneous semaglutide, dulaglutide, and efpeglenatide, all lowered the incidence of cardiovascular events. Liraglutide, oral semaglutide and exenatide once weekly also reduced mortality. GLP-1 RAs reduce the progression of diabetic kidney disease. In the 2019 consensus report from European Association for the Study of Diabetes/American Diabetes Association, GLP-1 RAs with demonstrated cardio-renal benefits (liraglutide, semaglutide and dulaglutide) are recommended after metformin to patients with established cardiovascular diseases or multiple cardiovascular risk factors. European Society of Cardiology suggests starting with a sodium-glucose cotransprter-2 inhibitor or a GLP-1 RA in drug naïve patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (CVD) or high CV Risk. However, the results from cardiovascular outcome trials (CVOT) are very heterogeneous suggesting that some GLP-1RAs are more suitable to prevent CVD than others. The CVOTs provide a basis upon which individual treatment decisions for patients with T2D and CVD can be made.
胰高血糖素样肽-1 受体激动剂 (GLP-1 RAs) 自 2005 年以来一直被用于治疗 2 型糖尿病患者，由于其在大多数患者中与血糖控制相关的疗效和持久性以及体重减轻，因此广受欢迎。如今，在 2022 年，有七种 GLP-1 RAs，包括口服司美格鲁肽，可用于治疗 2 型糖尿病。由于与 HbA1c 和体重降低相关的疗效以及耐受性和给药频率在不同药物之间存在差异，因此不能认为 GLP-1 RAs 是等同的。短效制剂利西那肽没有显示出心血管益处，而每日一次的利拉鲁肽和每周一次的激动剂，皮下司美格鲁肽、度拉糖肽和艾塞纳肽，都降低了心血管事件的发生率。利拉鲁肽、口服司美格鲁肽和艾塞那肽每周一次也降低了死亡率。GLP-1 RAs 可减缓糖尿病肾病的进展。在 2019 年欧洲糖尿病研究协会/美国糖尿病协会的共识报告中，具有心血管肾益处的 GLP-1 RAs（利拉鲁肽、司美格鲁肽和度拉糖肽）被推荐用于已患有心血管疾病或多种心血管危险因素的患者，作为二甲双胍治疗的替代药物。欧洲心脏病学会建议在药物初治的 2 型糖尿病（T2D）和动脉粥样硬化性心血管疾病（CVD）或高 CVD 风险患者中，起始使用钠-葡萄糖共转运蛋白-2 抑制剂或 GLP-1 RA。然而，心血管结局试验 (CVOT) 的结果非常不一致，表明一些 GLP-1RAs 比其他药物更适合预防 CVD。CVOT 为 2 型糖尿病合并 CVD 患者的个体化治疗决策提供了依据。
