Heile Michael, Wyne Kathleen, Billings Liana K, Cannon Anthony, Handelsman Yehuda, Shannon Michael
1 TriHealth, Cincinnati, Ohio.
2 The Ohio State University Wexner Medical Center, Columbus.
J Manag Care Spec Pharm. 2018 Sep;24(9-a Suppl):S42-S52. doi: 10.18553/jmcp.2018.24.9-a.s42.
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular (ASCVD) disease, which is the largest contributor to the economic burden of diabetes. Minimization of disease morbidity through comprehensive management of ASCVD risk factors, including but not limited to hyperglycemia, is a key goal of T2DM therapy. Emerging evidence with some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) points to beneficial effects across a range of atherosclerotic risk factors and possible improvement of some cardiovascular outcomes independent of these effects. Given these benefits, there has been substantial interest in evaluating the cardiovascular safety of GLP-1 RAs as well as their potential to reduce the risk of major adverse cardiac events (MACE). Following the superior clinical outcome with the once-daily GLP-1 RA liraglutide (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results [LEADER]), this review examines and summarizes the effects of once-weekly GLP-1 RAs, including exenatide extended release (ER), dulaglutide, and semaglutide, on reducing cardiovascular events in patients with T2DM. A phase 3 cardiovascular outcomes trial (EXSCEL) of exenatide ER found no significant difference between exenatide ER and placebo in reducing MACE in patients with T2DM. In a phase 3 premarketing trial in T2DM patients at high risk of cardiovascular disease (SUSTAIN-6), semaglutide significantly reduced the risks of MACE and non-fatal stroke compared with placebo. A phase 3 study (REWIND) is underway to evaluate the effects of dulaglutide on MACE. Considering the substantial costs of cardiovascular disease in patients with T2DM, it will be of interest to assess the impact of treatment with once-weekly GLP-1 RAs on cardiovascular disease-related costs among patients with T2DM.
This supplement was funded by Novo Nordisk. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Wyne has nothing to disclose.
2型糖尿病（T2DM）与动脉粥样硬化性心血管疾病（ASCVD）风险增加相关，这是糖尿病经济负担的最大贡献因素。通过全面管理ASCVD风险因素（包括但不限于高血糖）来尽量降低疾病发病率是T2DM治疗的关键目标。一些胰高血糖素样肽-1受体激动剂（GLP-1 RAs）的新证据表明，其对一系列动脉粥样硬化风险因素具有有益作用，并且可能独立于这些作用改善某些心血管结局。鉴于这些益处，人们对评估GLP-1 RAs的心血管安全性及其降低主要不良心脏事件（MACE）风险的潜力产生了浓厚兴趣。在每日一次的GLP-1 RA利拉鲁肽取得卓越临床结果之后（利拉鲁肽在糖尿病中的作用和效果：心血管结局评估结果[LEADER]），本综述研究并总结了每周一次的GLP-1 RAs，包括艾塞那肽缓释剂（ER）、度拉糖肽和司美格鲁肽，对降低T2DM患者心血管事件的影响。艾塞那肽ER的一项3期心血管结局试验（EXSCEL）发现，在降低T2DM患者的MACE方面，艾塞那肽ER与安慰剂之间无显著差异。在一项针对心血管疾病高风险T2DM患者的3期上市前试验（SUSTAIN-6）中，与安慰剂相比，司美格鲁肽显著降低了MACE和非致死性卒中的风险。一项评估度拉糖肽对MACE影响的3期研究（REWIND）正在进行中。考虑到T2DM患者心血管疾病的巨大成本，评估每周一次的GLP-1 RAs治疗对T2DM患者心血管疾病相关成本的影响将很有意义。
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