Emergency Medicine, Ohio State University, 6408 Phoenix Park Dr., Dublin, OH 43016, USA.
Postgrad Med. 2012 Nov;124(6):82-9. doi: 10.3810/pgm.2012.11.2614.
Many oral antidiabetic drugs (OADs) are available for patients with type 2 diabetes mellitus (T2DM). However, it is recognized that additional therapies are needed and several new compounds are in advanced stages of development.
This narrative review considers the essential features of a successful OAD, the main classes of OADs that are currently used, and the therapies that may be available in the upcoming years.
The first OADs (sulfonylureas and biguanides) were discovered by chance. Although effective in reducing blood glucose levels, early sulfonylureas were associated with significant off-target effects, and the biguanide phenformin was discontinued due to adverse events. Although metformin is in the same drug class, it has a better safety profile and is now recommended as first-line treatment, except when contraindicated. Nonetheless, many patients require additional glucose control (even on metformin) with an agent that has a complementary mechanism of action. Developments in bench science have facilitated the selection of agents for specific therapeutic targets, with the thiazolidinediones providing an interesting example. This OAD class initially appeared encouraging, yet in clinical practice was associated with safety concerns. As a result, newer agents, such as dipeptidyl peptidase-4 inhibitors, are undergoing more rigorous safety evaluations than OADs of previous generations. Promising compounds with novel mechanisms of action include the sodium-glucose co-transporter 2 inhibitors, the G-protein-coupled receptor agonists, and the balanced dual peroxisome proliferator-activated receptor-α/γ agonists. There is optimism that in the next few years, novel classes of OADs that are currently under development will offer additional blood glucose control options via complementary mechanisms of action. However, history has shown that compounds of the same class can have different safety profiles and treatment effects. Therefore, high-quality clinical trial evidence is needed for every compound.
有多种口服降糖药（OAD）可供 2 型糖尿病（T2DM）患者选择。然而，人们认识到需要额外的治疗方法，几种新的化合物也处于开发的后期阶段。
本综述叙述性地回顾了成功的 OAD 的基本特征、目前使用的 OAD 的主要类别，以及未来可能出现的治疗方法。
第一批 OAD（磺酰脲类和双胍类）是偶然发现的。虽然早期的磺酰脲类药物能有效降低血糖水平，但它们与显著的脱靶效应有关，二甲双胍因不良反应而被停用。尽管二甲双胍属于同一药物类别，但它具有更好的安全性，现在被推荐作为一线治疗药物，除非有禁忌症。尽管如此，许多患者仍需要使用具有互补作用机制的药物来控制血糖（即使在使用二甲双胍的情况下）。实验室科学的发展促进了针对特定治疗靶点的药物选择，噻唑烷二酮类药物就是一个很好的例子。这种 OAD 类药物最初看起来很有前景，但在临床实践中却存在安全问题。因此，与前几代 OAD 相比，新型药物，如二肽基肽酶-4 抑制剂，正在进行更严格的安全性评估。具有新型作用机制的有前途的化合物包括钠-葡萄糖共转运蛋白 2 抑制剂、G 蛋白偶联受体激动剂和平衡双重过氧化物酶体增殖物激活受体-α/γ激动剂。人们乐观地认为，在未来几年内，目前正在开发的新型 OAD 类药物将通过互补的作用机制提供额外的血糖控制选择。然而，历史表明，同一类别的化合物可能具有不同的安全性和治疗效果。因此，每种化合物都需要高质量的临床试验证据。
