Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy.
Diabetes Division, St Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
Diabetes Obes Metab. 2019 May;21(5):1081-1087. doi: 10.1111/dom.13629. Epub 2019 Feb 14.
An excess risk of heart failure (HF) persists in patients with type 2 diabetes (T2D) despite optimal control of an array of conventional risk factors, including hyperglycaemia. Twelve cardiovascular outcome trials (CVOTs) have been published to date, although none, with the exception of the DECLARE trial with dapagliflozin, has included HF as a primary endpoint. The four trials with dipeptidyl-peptidase inhibitors (DPP-4i) (SAVOR-TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin and CARMELINA with linagliptin) failed to show any significant effect on HF risk in patients with T2D, with the notable exception of saxagliptin which was associated with a 27% increased risk. Five completed CVOTs with the GLP-1 RAs lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), exenatide once weekly (EXSCEL) and albiglutide (HARMONY) also failed to reveal any significant effect on HF risk. The three trials with sodium glucose co-transporter-2 inhibitors (SGLT-2i) (EMPA-REG OUTCOME with empagliflozin, CANVAS with canagliflozin and DECLARE with dapagliflozin) all revealed a robust and significant reduction in the hazard ratios of hospitalization for HF, from 27% to 35%, which remained consistent, significant and of similar magnitude regardless of the presence of a history of HF or established atherosclerotic cardiovascular disease. There is no association between reductions in HF risk and haemoglobin A1c (A1C) levels, while there is a significant association between reductions in HR for MACE and A1C levels (Spearman's correlation, r = 0.695; P = 0.013). All of the 12 CVOTs completed to date have provided reassurance of the overall cardiovascular safety of the newer anti-hyperglycaemic drugs. At present, the robust, consistent and reproducible reduction of approximately 30% in the risk of HF with SGLT-2i may be considered a class effect. The beneficial effect on MACE outcome observed with the use of some GLP-1RAs and SGLT-2i must be interpreted within the frame of the single trial.
尽管 2 型糖尿病 (T2D) 患者的一系列传统危险因素（包括高血糖）得到了最佳控制，但心力衰竭 (HF) 的风险仍然过高。迄今为止，已经发表了 12 项心血管结局试验 (CVOT)，但除了达格列净的DECLARE 试验外，没有一项试验将 HF 作为主要终点。四项二肽基肽酶-4 抑制剂 (DPP-4i) 试验（沙格列汀的 SAVOR-TIMI 53、阿格列汀的 EXAMINE、西格列汀的 TECOS 和利格列汀的 CARMELINA）均未能显示 T2D 患者 HF 风险有任何显著影响，只有沙格列汀例外，其风险增加了 27%。五项已完成的 GLP-1 RA 试验（lixisenatide [ELIXA]、liraglutide [LEADER]、semaglutide [SUSTAIN-6]、艾塞那肽每周一次 [EXSCEL] 和 albiglutide [HARMONY]）也未能显示 HF 风险有任何显著影响。三项钠-葡萄糖协同转运蛋白-2 抑制剂 (SGLT-2i) 试验（empagliflozin 的 EMPA-REG OUTCOME、canagliflozin 的 CANVAS 和达格列净的 DECLARE）均显示 HF 住院风险的危险比显著降低 27%至 35%，且无论是否存在 HF 病史或已确诊的动脉粥样硬化性心血管疾病，该结果均一致、显著且具有相似幅度。HF 风险降低与糖化血红蛋白 (A1C) 水平之间没有关联，而 MACE 和 A1C 水平的 HR 降低之间存在显著关联（Spearman 相关系数，r=0.695；P=0.013）。迄今为止，所有 12 项已完成的 CVOT 都为新型抗高血糖药物的整体心血管安全性提供了保证。目前，SGLT-2i 可显著、一致且可重复地降低 HF 风险约 30%，可被视为一种类效应。使用某些 GLP-1RA 和 SGLT-2i 观察到的对 MACE 结局的有益影响必须在单一试验的框架内进行解释。
