腸泌素類藥物與第2型鈉葡萄糖轉運蛋白抑制劑對於糖尿病腎疾病的效益與限制

Benefits and Limitations of Incretin-Based Therapies and Sodium-Glucose Transporter 2 Inhibitors on Diabetic Kidney Disease

林義智(Yi-Chih Lin) ； 楊紹佑(Shao-Yu Yang)

《內科學誌》 27卷5期 (2016/10) Pp. 248-260

https://doi.org/10.6314/JIMT.2016.27(5).04

摘要

糖尿病腎疾病是糖尿病患者主要死因之一，也是造成全世界末期腎疾病最主要的原因。糖尿病腎疾病是臨床症候群，其特色包括持續性白蛋白尿(每天尿中白蛋白量超過300 毫克)、腎絲球濾過率的持續降低、動脈血壓的上升、心血管事件的增加以及因心血管事件死亡率的上升。在台灣地區，糖尿病患者是新發生透析個案中最主要的族群，且發生透析患者中的糖尿病人數近年來仍逐漸增加中，透析患者合併有糖尿病者死亡率也較高。糖尿病腎疾病的危險因子在許多研究中已被釐清，近期研究結果也證實血糖控制可減緩腎功能的惡化，並避免併發症的發生。雖然過去已有許多種降血糖藥物，但臨床上血糖控制可達標準的患者仍有限，而低血糖和體重增加等藥物副作用也使得血糖的治療受到限制。近年來發展出更新式的口服降血糖藥物，可改善血糖控制，並避免進一步糖尿病腎病變的發生及惡化。本文將著重回顧近期實驗室細胞實驗、動物實驗以及人體試驗相關的研究成果中，腸泌素類藥物與第2型鈉葡萄糖轉運蛋白抑制劑對於糖尿病腎疾病及腎臟保護的效益及其限制。

關鍵字

糖尿病腎疾病(Diabetic kidney disease，簡稱DKD) ； 糖尿病腎病變(Diabetic nephropathy，簡稱DN) ； 糖尿病(Diabetes mellitus) ； 雙基胜肽酶-4 抑制劑(Dipeptidyl dipeptidase 4 inhibitors，簡稱DPP4 inhibitors) ； 似升糖素胜肽-1 受體促進劑或類似物 (Glucagon-like peptide 1 receptor agonist or analogue，簡稱GLP-1 receptor agonist or analogue) ； 第2型鈉-葡萄糖轉運蛋白抑制劑(Sodium glucose transporter 2 inhibitors，簡稱SGLT2 inhibitors)

並列摘要

Diabetic kidney disease (DKD) is one of major causes of mortality in patients with diabetes mellitus and is also the leading cause of end-stage renal disease in the world. DKD is a clinical syndrome, characterized by persistent albuminuria (daily urine protein loss ＞300 minigram), declined glomerular filtration rate, arterial pressure elevation, increase cardiovascular events and mortality rate. In Taiwan, the major group of incidental dialysis is patients with diabetes mellitus. The number of receiving dialysis patients with diabetes mellitus is still increasing up to date. Besides, patients with diabetes and receiving dialysis have higher mortality than those without diabetes. Risk factors of DKD include ethics, sex, albuminuria, hyperglycemia, hypertension, dyslipidemia, hypercholesterolemia, smoking, gene susceptibility, etc. More recent researches have proved that adequate blood sugar control prevents from occurrence of complications and relieve progression of DKD. Although there are many kinds of blood glucose-lowering drugs in the past decades, the number of people achieving goals of blood sugar control is still limited. Moreover, the side effects of these drugs, such as hypoglycemia and weight gain restrict the blood glucose control. Hence, novel blood glucose-lowering drugs and options were developed in recent years for prevention of progressive nephropathy. This article emphasizes on benefits and limitations of incretin-based therapies and sodium-glucose transporter 2 inhibitors by reviewing current animal, laboratory and human researches.