Centre of Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK.
Lancet. 2011 Jul 9;378(9786):182-97. doi: 10.1016/S0140-6736(11)60207-9. Epub 2011 Jun 24.
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 11β-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.
2 型糖尿病的患病率不断上升、发病机制多样、自然病程进展以及并发症，强调了迫切需要新的治疗策略。胰高血糖素样肽-1 受体的长效（例如，每周一次）激动剂正在开发中，它们可改善餐时胰岛素分泌，减少多余的胰高血糖素产生，并促进饱腹感。二肽基肽酶 4 抑制剂的试验也即将完成，这些抑制剂可增强内源性肠促胰岛素激素的作用。血糖调节的新方法包括使用钠-葡萄糖共转运蛋白 2 抑制剂，增加肾脏葡萄糖清除率，以及 11β-羟类固醇脱氢酶 1 抑制剂，减少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动剂和胰腺 G 蛋白偶联脂肪酸受体激动剂、胰高血糖素受体拮抗剂以及肝脏葡萄糖输出的代谢抑制剂。已证明增强并部分模拟胰岛素作用并复制部分减重手术效果的化合物具有早期原理验证。
