Management of type 2 diabetes: new and future developments in treatment
Management of type 2 diabetes: new and future developments in treatment
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DOI：
10.1016/s0140-6736(11)60207-9
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发表时间：
2011-07-09
期刊：
影响因子：
168.9
通讯作者：
Barnett, Anthony H.
中科院分区：
文献类型：
--
作者：
Tahrani, Abd A.;Bailey, Clifford J.;Barnett, Anthony H.
2型糖尿病日益增加的患病率、多变的发病机制、渐进的自然史和并发症强调了对新治疗策略的迫切需要。胰高血糖素样肽-1受体的长效（例如，每周一次）激动剂在开发中处于晚期，它们改善餐时胰岛素分泌，减少胰高血糖素的过量产生，并促进饱腹感。增强内源性肠促胰岛素激素作用的二肽基肽酶4抑制剂的试验也接近完成。调节血糖的新方法包括使用钠葡萄糖协同转运蛋白2抑制剂（可增加肾脏葡萄糖消除）和11 β-羟基类固醇脱氢酶1抑制剂（可降低肝脏和脂肪中的糖皮质激素作用）。正在评估胰岛素释放葡萄糖激酶激活剂和胰腺G蛋白偶联脂肪酸受体激动剂、胰高血糖素受体拮抗剂和肝葡萄糖输出代谢抑制剂。早期的原理证明已经显示出增强和部分模拟胰岛素作用并复制减肥手术的一些效果的化合物。
The increasing prevalence, variable pathogenesis, progressive natural history, and complications of type 2 diabetes emphasise the urgent need for new treatment strategies. Longacting (eg, once weekly) agonists of the glucagon-like-peptide-1 receptor are advanced in development, and they improve prandial insulin secretion, reduce excess glucagon production, and promote satiety. Trials of inhibitors of dipeptidyl peptidase 4, which enhance the effect of endogenous incretin hormones, are also nearing completion. Novel approaches to glycaemic regulation include use of inhibitors of the sodium glucose cotransporter 2, which increase renal glucose elimination, and inhibitors of 11 beta-hydroxysteroid dehydrogenase 1, which reduce the glucocorticoid effects in liver and fat. Insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, and metabolic inhibitors of hepatic glucose output are being assessed. Early proof of principle has been shown for compounds that enhance and partly mimic insulin action and replicate some effects of bariatric surgery.