CPCLIN - Centro de Pesquisas Clínicas, Av. Angélica, 2162 - Consolação, São Paulo, SP, 01228-200, Brazil.
Curr Atheroscler Rep. 2022 Nov;24(11):867-884. doi: 10.1007/s11883-022-01062-2. Epub 2022 Aug 31.
To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk.
Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3 mg/day liraglutide program and the STEP 2.4 mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.
讨论胰高血糖素样肽 1 受体激动剂（GLP-1RA）治疗肥胖的证据及其作为心脏保护药物的作用。肥胖不仅仅是脂肪组织的肥大，因为它可能变得功能失调和炎症，导致胰岛素抵抗增加。超重与心血管事件发生率增加有关，通过生活方式改变减肥可以降低风险因素，但对心血管结局没有明显影响。相比之下，用 GLP-1RA 治疗肥胖可以降低心血管风险，讨论了这类药物实现的心脏保护的可能机制。GLP-1RA 最初是为治疗 2 型糖尿病患者而开发的，在这些患者中，对血糖的影响，而且，体重减轻，特别是长效 GLP-1RA，是显而易见的。然而，在 2 型糖尿病患者中的心血管安全性试验中，大多数患者患有心血管疾病和超重，表明 GLP-1 受体激动剂确实能够降低心血管风险。
GLP-1RA 利拉鲁肽和司美格鲁肽治疗 2 型糖尿病为肥胖症开辟了一种突破性的治疗方法，如 SCALE 3mg/天利拉鲁肽计划和 STEP 2.4mg/周司美格鲁肽计划所示。一种具有卓越性能的新型分子是替西帕肽，一种 GLP-1 和 GIP（胃抑制肽）受体激动剂，简要描述了最近 SURPASS 和 SURMOUNT 计划的结果。利拉鲁肽在没有心血管结局试验（CVOT）的情况下获得批准，因为当局接受了旨在卓越的 LEADER 研究的结果。司美格鲁肽的 SELECT 研究将仅在 2023 年报告结果，而替西帕肽正在糖尿病患者中进行 SURPASS-CVOT 测试。临床研究强调，GLP-1RA 治疗肥胖症及其伴随的心脏保护作用已成为临床科学的标志。
