Sivakumar Ponnurengam Malliappan, Premkumar B, Prabhawathi Veluchamy, Prabhakar Pranav Kumar
Center for Molecular Biology, Institute of Research and Development, Duy Tan University, Da Nang, Vietnam.
Department of Pharmacology, K. K College of Pharmacy, Gerugambakkam, Chennai, Tamil Nadu, India.
Mini Rev Med Chem. 2021;21(20):3166-3182. doi: 10.2174/1389557521666210422114909.
The cardiovascular complications of Type 2 Diabetes Mellitus (T2DM) including myocardial infarction, heart failure, peripheral vascular disease and, stroke and retinopathy, nephropathy and neuropathy are microvascular complications. While the newer therapies like glitazones or even Dipeptidyl- peptidase-IV (DPP-IV) inhibitors increase the risk of therapy, the Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs), were reported as suitable alternates. The GLP-1RAs reduce Major Adverse Cardiovascular Events (MACE), have anti-atherogenic potential, and possess pleiotropic activity. The GLP-1RAs were found to improve neuroprotection, enhance neuronal growth, reduce the incidence of stroke, and improve central insulin resistance. The GLP-1RAs are beneficial in improving the glycemic profile, preventing macroalbuminuria and reducing the decline in eGFR and enhancing renal protection. The renal benefits of add-on therapy of GLP-1RAs with SGLT-2 inhibitors have composite renal outcomes such as suppression of inflammatory pathways, improvement in natriuresis, diuresis, found to be nephroprotective. Improvement in glycemic control with a reduction in body weight and intraglomerular pressure and prevention of tubular injury makes the GLP-1RAs as suitable add-on therapies in improving cardiorenal outcomes. Obesity, an important contributor to insulin resistance and a reduction in weight, is an essential therapeutic option in addressing diabetic-obesity. It also reduces the damage to blood-retinal-barrier, thus beneficial in halting the development of diabetic retinopathy. In diabetic complications, glycemic control, addressing insulin resistance through weight loss, controlling atherosclerosis through anti-inflammatory effects and cardio-renal-neuro protection, makes GLP-1RAs a suitable therapeutic strategy on long-term treatment of T2DM. This review discusses the role of GLP-1RAs in diabetes, the dosage, mono or combination therapy with other antidiabetics in long-term treatment and its effect in uncontrolled diabetes.
2型糖尿病（T2DM）的心血管并发症包括心肌梗死、心力衰竭、外周血管疾病、中风，而视网膜病变、肾病和神经病变则属于微血管并发症。虽然像格列酮类甚至二肽基肽酶-4（DPP-IV）抑制剂等新型疗法会增加治疗风险，但胰高血糖素样肽-1受体激动剂（GLP-1RAs）被报道为合适的替代药物。GLP-1RAs可降低主要不良心血管事件（MACE），具有抗动脉粥样硬化潜力，并具有多效活性。研究发现，GLP-1RAs可改善神经保护作用、促进神经元生长、降低中风发生率并改善中枢胰岛素抵抗。GLP-1RAs有助于改善血糖状况、预防大量蛋白尿、减少估算肾小球滤过率（eGFR）下降并增强肾脏保护作用。GLP-1RAs与钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂联合治疗的肾脏益处具有复合肾脏结局，如抑制炎症途径、改善尿钠排泄和利尿作用，被发现具有肾脏保护作用。通过改善血糖控制、减轻体重和降低肾小球内压力以及预防肾小管损伤，使得GLP-1RAs成为改善心肾结局的合适联合治疗药物。肥胖是胰岛素抵抗的重要因素且减轻体重是治疗糖尿病肥胖的重要治疗选择。它还可减少对血视网膜屏障的损害，因此有助于阻止糖尿病视网膜病变的发展。在糖尿病并发症中，通过控制血糖、减轻体重来解决胰岛素抵抗、通过抗炎作用控制动脉粥样硬化以及进行心肾神经保护，使得GLP-1RAs成为T2DM长期治疗的合适治疗策略。本综述讨论了GLP-1RAs在糖尿病中的作用、剂量、与其他抗糖尿病药物的单药或联合治疗在长期治疗中的应用及其在未控制糖尿病中的效果。
