Eli Lilly Italia, Sesto Fiorentino, Italy.
Asl3 Genovese, Head of Endocrinology, Diabetology and Metabolic Diseases SSD, Genova, Italy.
Diabetes Metab Res Rev. 2021 Oct;37(7):e3434. doi: 10.1002/dmrr.3434. Epub 2021 Feb 7.
Despite the importance of individualised strategies for patients with type 2 diabetes mellitus (T2DM) and the availability of alternative treatments, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sulphonylureas are still widely used in practice. Clinical evidence shows that GLP-1 RAs may provide better and more durable glycaemic control than sulphonylureas, with lower risk of hypoglycaemia. Other reported benefits of GLP-1 RAs include weight loss rather than weight gain (as observed with sulphonylureas), blood pressure reduction and improvement in lipid profiles. In general, the main adverse events with GLP-1 RAs are gastrointestinal in nature. The respective modes of action of GLP-1 RAs and sulphonylureas contribute to differences in the durability of glycaemic control (related to effects on beta-cells) and effects on body weight. Moreover, the glucose-dependent mode of action of GLP-1 RAs, which favours a low incidence of hypoglycaemia, contrasts with the glucose-independent mode of action of sulphonylureas. Evidence from cardiovascular outcomes trials indicates a consistent finding of cardiovascular safety across the GLP-1 RAs and suggests a class benefit for the long-acting GLP-1 RAs in reducing three-point major adverse cardiovascular events, cardiovascular mortality and all-cause mortality. In contrast, potential concerns relating to an increased incidence of adverse cardiovascular events with sulphonylureas have yet to be fully resolved. Recent updates to management guidelines recommend that treatment selection for patients with T2DM should consider clinical trial evidence of cardiovascular safety. Available evidence suggests that this selection should give preference to GLP-1 RAs over sulphonylureas, especially for patients at high cardiovascular risk.
尽管对于 2 型糖尿病(T2DM)患者来说,制定个体化策略非常重要,而且有替代治疗方法,包括胰高血糖素样肽-1 受体激动剂(GLP-1 RAs),磺酰脲类药物在实践中仍被广泛使用。临床证据表明,GLP-1 RAs 可能比磺酰脲类药物提供更好、更持久的血糖控制,低血糖风险更低。GLP-1 RAs 还具有其他益处,包括体重减轻而不是体重增加(磺酰脲类药物则会导致体重增加)、血压降低和血脂谱改善。一般来说,GLP-1 RAs 的主要不良反应是胃肠道性质的。GLP-1 RAs 和磺酰脲类药物的作用机制不同,导致血糖控制的持久性(与β细胞的作用有关)和对体重的影响不同。此外,GLP-1 RAs 的葡萄糖依赖性作用机制有利于低血糖的低发生率,与磺酰脲类药物的葡萄糖非依赖性作用机制形成对比。来自心血管结局试验的证据表明,GLP-1 RAs 在心血管安全性方面具有一致的发现,并表明长效 GLP-1 RAs 具有降低三点主要不良心血管事件、心血管死亡率和全因死亡率的类效应益处。相比之下,磺酰脲类药物可能会增加不良心血管事件的发生率,这一问题尚未得到充分解决。最近更新的管理指南建议,T2DM 患者的治疗选择应考虑心血管安全性的临床试验证据。现有证据表明,这种选择应优先选择 GLP-1 RAs 而不是磺酰脲类药物,尤其是对于心血管风险高的患者。