Clinical Pharmacology Unit, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège and Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU de Liège, CHU Sart Tilman (B35), 4000 Liège 1, Belgium.
Diabetology and Nutrition Unit, GIGA-I3, University of Liege, and Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU de Liège, Liège, Belgium.
Diabetes Metab. 2015 Jun;41(3):183-94. doi: 10.1016/j.diabet.2015.02.003. Epub 2015 Mar 18.
A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to chronic inflammation. These observations pave the way to the development of new pharmacological strategies that aim to reduce silent inflammation. However, besides specific anti-inflammatory agents, glucose-lowering medications may also exert anti-inflammatory effects that could contribute to improved outcomes in diabetic patients. Most studies have used metformin, an AMP-activated protein kinase (AMPK) activator, and thiazolidinediones (TZDs), which act as peroxisome proliferator-activated receptor-gamma (PPARγ) agonists. Both pharmacological classes (considered insulin-sparing agents or insulin sensitizers) appear to have greater anti-inflammatory activity than insulin-secreting agents such as sulphonylureas or glinides. In particular, TZDs have shown the widest range of evidence of lowered tissue (visceral fat and liver) and serum inflammation. In contrast, despite reducing postprandial hyperglycaemia, the effect of α-glucosidase inhibitors on inflammatory markers appears rather modest, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and glucagon-like peptide-1 (GLP-1) receptor agonists appear more promising in this respect. These incretin-based therapies exert pleiotropic effects, including reports of anti-inflammatory activity. No human data are available so far regarding sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Although they may have indirect effects due to reduced glucotoxicity, their specific mode of action in the kidneys does not suggest systemic anti-inflammatory activity. Also, in spite of the complex relationship between insulin and atherosclerosis, exogenous insulin may also exert anti-inflammatory effects. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and potential anti-inflammatory effects related to intrinsic actions of the pharmacological class. Finally, it would also be of major clinical interest to define what role the anti-inflammatory effects of these glucose-lowering agents may play in the prevention of macrovascular and microvascular diabetic complications.
越来越多的证据表明，腹部肥胖、代谢综合征、2 型糖尿病、心血管疾病和微血管糖尿病并发症与慢性炎症密切相关。这些观察结果为开发旨在减轻沉默炎症的新药理策略铺平了道路。然而，除了特定的抗炎剂外，降血糖药物也可能发挥抗炎作用，从而改善糖尿病患者的预后。大多数研究都使用了二甲双胍（一种 AMP 激活蛋白激酶（AMPK）激活剂）和噻唑烷二酮类药物（TZDs），它们作为过氧化物酶体增殖物激活受体-γ（PPARγ）激动剂。这两类药物（被认为是胰岛素增敏剂或胰岛素增敏剂）似乎比磺酰脲类或格列奈类等胰岛素分泌剂具有更强的抗炎活性。特别是，TZDs 显示出降低组织（内脏脂肪和肝脏）和血清炎症的最广泛证据。相比之下，尽管α-葡萄糖苷酶抑制剂可以降低餐后高血糖，但它们对炎症标志物的影响似乎相当温和，而二肽基肽酶-4（DPP-4）抑制剂（gliptins）和胰高血糖素样肽-1（GLP-1）受体激动剂在这方面似乎更有前途。这些基于肠促胰岛素的治疗方法具有多种作用，包括抗炎活性的报道。到目前为止，还没有关于钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂的人体数据。尽管由于减少了葡萄糖毒性，它们可能具有间接作用，但它们在肾脏中的特定作用方式并不能表明具有全身抗炎活性。此外，尽管胰岛素与动脉粥样硬化之间存在复杂的关系，但外源性胰岛素也可能发挥抗炎作用。然而，对于所有这些降血糖药物，区分更好的血糖控制导致的抗炎作用和药理学作用的内在作用相关的潜在抗炎作用是至关重要的。最后，确定这些降血糖药物的抗炎作用在预防大血管和微血管糖尿病并发症方面可能发挥的作用也具有重要的临床意义。
