University of Liverpool, Aintree University Hospital NHS Foundation Trust, Clinical Sciences Centre, Department of Obesity & Endocrinology, Longmoor Lane, Liverpool L9 7AL, UK.
Expert Opin Emerg Drugs. 2013 Sep;18(3):375-91. doi: 10.1517/14728214.2013.831405.
Type 2 diabetes mellitus (T2DM) is a public health challenge globally. Numerous treatments are available which can improve insulin sensitivity or stimulate its secretion including biguanides, sulphonylureas and glitazones, as well as insulin, GLP-1 agonists and DPP-IV inhibitors. These are usually unable to halt progression with high resulting morbidity and mortality. New therapies are, therefore, being developed; inhibition of glucose reabsorption from the renal filtrate has been proposed as a novel therapeutic target, and sodium/glucose co-transporter 2 (SGLT2) inhibitors have been developed accordingly.
This review summarises the challenge that T2DM poses and describes established therapies. The market for these therapies and likely changes are examined, as well as the scientific rationale behind the development of SGLT2 inhibitors. SGLT2 inhibitors in clinical trials worldwide are reviewed and issues affecting their development are discussed.
SGLT2 inhibitors offer a novel therapeutic approach to the management of T2DM; advantages over other agents include weight loss and blood pressure lowering with a low intrinsic risk of hypoglycaemia. The main adverse effects likely to be seen in clinical practice are a very small increase in risk of urinary tract infections, and a modest risk of developing genital fungal infections - which appear more common in the first few months of treatment. Meta-analyses suggest no increased risk of cardiovascular disease, but longer duration outcome studies are essential to prove long-term safety and efficacy.
2 型糖尿病（T2DM）是一个全球性的公共卫生挑战。有许多治疗方法可以改善胰岛素敏感性或刺激其分泌，包括双胍类、磺酰脲类和噻唑烷二酮类，以及胰岛素、GLP-1 激动剂和 DPP-IV 抑制剂。这些方法通常无法阻止病情进展，导致高发病率和死亡率。因此，正在开发新的治疗方法；从肾滤液中抑制葡萄糖重吸收已被提议作为一种新的治疗靶点，并且已经开发了相应的钠/葡萄糖协同转运蛋白 2（SGLT2）抑制剂。
本文综述了 T2DM 带来的挑战，并描述了已确立的治疗方法。审查了这些治疗方法的市场及其可能的变化，以及开发 SGLT2 抑制剂的科学依据。回顾了全球临床试验中的 SGLT2 抑制剂，并讨论了影响其开发的问题。
SGLT2 抑制剂为 T2DM 的治疗提供了一种新的治疗方法；与其他药物相比，其优点包括减轻体重和降低血压，且低血糖风险低。在临床实践中可能出现的主要不良反应是尿路感染风险略有增加，以及生殖真菌感染的风险适度增加 - 这些不良反应在治疗的头几个月更为常见。荟萃分析表明心血管疾病风险没有增加，但需要进行更长期的结局研究以证明长期安全性和疗效。
