Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands.
Nat Rev Nephrol. 2014 Feb;10(2):88-103. doi: 10.1038/nrneph.2013.272. Epub 2013 Dec 24.
Diabetic nephropathy is the leading cause of end-stage renal disease worldwide, and is associated with a high risk of cardiovascular morbidity and mortality. Intensive control of glucose levels and blood pressure is currently the mainstay of both prevention and treatment of diabetic nephropathy. However, this strategy cannot fully prevent the development and progression of diabetic nephropathy, and an unmet need remains for additional novel therapies. The incretin-based agents--agonists of glucagon-like peptide 1 receptor (GLP-1R) and inhibitors of dipeptidyl peptidase 4 (DPP-4), an enzyme that degrades glucagon-like peptide 1--are novel blood-glucose-lowering drugs used in the treatment of type 2 diabetes mellitus (T2DM). Therapeutic agents from these two drug classes improve pancreatic islet function and induce extrapancreatic effects that ameliorate various phenotypic defects of T2DM that are beyond glucose control. Agonists of GLP-1R and inhibitors of DPP-4 reduce blood pressure, dyslipidaemia and inflammation, although only GLP-1R agonists decrease body weight. Both types of incretin-based agents inhibit renal tubular sodium reabsorption and decrease glomerular pressure as well as albuminuria in rodents and humans. In rodents, incretin-based therapies also prevent onset of the morphological abnormalities of diabetic nephropathy.
糖尿病肾病是全球范围内导致终末期肾病的主要原因，与心血管发病率和死亡率升高相关。目前，严格控制血糖水平和血压是预防和治疗糖尿病肾病的主要方法。然而，这种策略并不能完全预防糖尿病肾病的发生和进展，因此仍然需要额外的新型治疗方法。基于肠促胰岛素的药物——胰高血糖素样肽 1 受体（GLP-1R）激动剂和二肽基肽酶 4（DPP-4）抑制剂，是用于治疗 2 型糖尿病（T2DM）的新型降血糖药物。这两类治疗药物可改善胰岛功能，并发挥胰外作用，改善 T2DM 的各种表型缺陷，而不仅仅是控制血糖。GLP-1R 激动剂和 DPP-4 抑制剂可降低血压、血脂异常和炎症，尽管只有 GLP-1R 激动剂可减轻体重。这两种肠促胰岛素药物均可抑制啮齿动物和人类的肾小管钠重吸收，并降低肾小球压和蛋白尿。在啮齿动物中，肠促胰岛素治疗还可预防糖尿病肾病的形态学异常的发生。
