Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
The Welch Center for Prevention, Epidemiology, and Clinical Research, 2024 E. Monument Street, Suite 2-600 (Rm 2-203), Baltimore, MD, 21287, USA.
Curr Diab Rep. 2019 Jul 8;19(8):54. doi: 10.1007/s11892-019-1171-0.
There is consensus that metformin should be the first-line pharmacological therapy for type 2 diabetes. Although new evidence on effective treatments for type 2 diabetes is rapidly evolving, there is uncertainty regarding the optimal choice of second-line therapy. Our aim was to review the current major guidelines for second-line therapy in type 2 diabetes, along with findings from the recent cardiovascular outcome trials, focusing on two particularly promising classes of glucose-lowering drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP1 RAs).
In the recent randomized controlled trials, two SGLT2 inhibitors (i.e., empagliflozin and canagliflozin) and two GLP1 RAs (i.e., liraglutide and albiglutide) reduced cardiovascular events in patients with type 2 diabetes, of whom most had established atherosclerotic cardiovascular disease. Some clinical guidelines have changed their recommendations for second-line therapy based on these findings. The first choice for a second-line therapy by the new American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) guidelines is SGLT2 inhibitors or GLP1 RAs for patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. For patients without these conditions, the ADA/EASD lists five options of noninsulin second-line therapy without a suggested hierarchy of use. On the other hand, the 2019 consensus statement from the American Association of Clinical Endocrinologists/American College of Endocrinology lists nine hierarchical options, with GLP1 RAs as the first recommended therapy, followed by SGLT2 inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors, and sulfonylurea as the last option. The American College of Physicians recommends four oral treatment options, which do not include GLP1 RAs. The International Diabetes Federation recommends sulfonylureas, DPP4 inhibitors, or SGLT2 inhibitors as preferred second-line drugs with GLP1 RAs as an alternative in obese patients. The World Health Organization strongly recommends sulfonylureas in low-resource settings. The National Institute for Health and Care Excellence in the UK recommends DPP4 inhibitors, thiazolidinediones, or sulfonylureas, with use of SGLT2 inhibitors only under special circumstances. Clinical guidelines for the choice of second-line therapy in type 2 diabetes are inconsistent. A comprehensive assessment of the risks and benefits of second-line therapy is needed to address knowledge gaps that underlie core clinical practice.
二甲双胍被认为是 2 型糖尿病的一线药物治疗。虽然新的 2 型糖尿病有效治疗方法的证据不断涌现，但二线治疗的最佳选择仍存在不确定性。我们的目的是综述当前 2 型糖尿病二线治疗的主要指南，以及最近心血管结局试验的结果，重点关注两类特别有前途的降糖药物，即钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂和胰高血糖素样肽 1 受体激动剂（GLP1 RAs）。
在最近的随机对照试验中，两种 SGLT2 抑制剂（即恩格列净和卡格列净）和两种 GLP1 RAs（即利拉鲁肽和阿必鲁肽）降低了有 2 型糖尿病且大多患有动脉粥样硬化性心血管疾病的患者的心血管事件。一些临床指南根据这些发现改变了二线治疗的建议。新的美国糖尿病协会/欧洲糖尿病研究协会（ADA/EASD）指南对有动脉粥样硬化性心血管疾病、心力衰竭或慢性肾脏病的患者的二线治疗的首选是 SGLT2 抑制剂或 GLP1 RAs。对于没有这些情况的患者，ADA/EASD 列出了五种非胰岛素二线治疗选择，没有建议的使用层次结构。另一方面，美国临床内分泌医师协会/美国内分泌学会 2019 年共识声明列出了九个分层选择，将 GLP1 RAs 作为首选治疗，其次是 SGLT2 抑制剂和二肽基肽酶 4（DPP4）抑制剂，磺酰脲类作为最后选择。美国医师学院推荐四种口服治疗选择，其中不包括 GLP1 RAs。国际糖尿病联合会建议将磺酰脲类、DPP4 抑制剂或 SGLT2 抑制剂作为首选二线药物，肥胖患者可选择 GLP1 RAs。世界卫生组织强烈建议在资源有限的环境中使用磺酰脲类药物。英国国家卫生与保健优化研究所建议使用 DPP4 抑制剂、噻唑烷二酮类或磺酰脲类药物，只有在特殊情况下才使用 SGLT2 抑制剂。2 型糖尿病二线治疗选择的临床指南不一致。需要全面评估二线治疗的风险和益处，以解决核心临床实践背后的知识差距。
