3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Cardiovascular Division, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Curr Pharm Des. 2023;29(23):1844-1862. doi: 10.2174/1381612829666230703161058.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with diabetes mellitus (DM). Although benefit has been attributed to the strict control of hyperglycemia with traditional antidiabetic treatments, novel antidiabetic medications have demonstrated cardiovascular (CV) safety and benefits by reducing major adverse cardiac events, improving heart failure (HF), and decreasing CVD-related mortality. Emerging data underline the interrelation between diabetes, as a metabolic disorder, and inflammation, endothelial dysfunction, and oxidative stress in the pathogenesis of microvascular and macrovascular complications. Conventional glucose-lowering medications demonstrate controversial CV effects. Dipeptidyl peptidase- 4 inhibitors have not only failed to prove to be beneficial in patients with coronary artery disease, but also their safety is questionable for the treatment of patients with CVD. However, metformin, as the first-line option for type 2 DM (T2DM), shows CVD protective properties for DM-induced atherosclerotic and macrovascular complications. Thiazolidinedione and sulfonylureas have questionable effects, as evidence from large studies shows a reduction in the risk of CV events and deaths, but with an increased rate of hospitalization for HF. Moreover, several studies have revealed that insulin monotherapy for T2DM treatment increases the risk of major CV events and deaths from HF, when compared to metformin, although it may reduce the risk of myocardial infarction. Finally, this review aimed to summarize the mechanisms of action of novel antidiabetic drugs acting as glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors that show favorable effects on blood pressure, lipid levels, and inflammation, leading to reduced CVD risk in T2DM patients.
心血管疾病(CVD)是糖尿病患者发病率和死亡率的主要原因。虽然传统的抗糖尿病治疗通过严格控制高血糖已经带来了益处,但新型抗糖尿病药物通过减少主要不良心脏事件、改善心力衰竭(HF)和降低 CVD 相关死亡率,已经证明了其心血管(CV)安全性和益处。新出现的数据强调了糖尿病作为一种代谢紊乱与炎症、内皮功能障碍和氧化应激之间的相互关系,这些都在微血管和大血管并发症的发病机制中发挥作用。传统的降血糖药物对 CV 的影响存在争议。二肽基肽酶-4 抑制剂不仅未能证明对冠心病患者有益,而且其在 CVD 患者中的治疗安全性也存在疑问。然而,二甲双胍作为 2 型糖尿病(T2DM)的一线治疗药物,对 DM 引起的动脉粥样硬化和大血管并发症具有心血管保护作用。噻唑烷二酮和磺酰脲类药物的作用存在争议,因为大型研究的证据表明,它们可以降低 CV 事件和 HF 死亡的风险,但 HF 的住院率增加。此外,几项研究表明,与二甲双胍相比,胰岛素单独用于 T2DM 治疗会增加 HF 引起的主要 CV 事件和死亡风险,尽管它可能降低心肌梗死的风险。最后,本综述旨在总结作为胰高血糖素样肽-1 受体激动剂和钠-葡萄糖共转运蛋白-2 抑制剂的新型抗糖尿病药物的作用机制,这些药物对血压、血脂水平和炎症有有利影响,从而降低 T2DM 患者的 CVD 风险。