Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal; Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal.
Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal; Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal.
J Am Coll Cardiol. 2023 Aug 8;82(6):517-525. doi: 10.1016/j.jacc.2023.05.048.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP-1 RAs) reduce adverse cardiovascular outcomes in type 2 diabetes (T2D). However, the efficacy of combination therapy is unclear.
The aim of this study was to evaluate the effects of GLP-1 RAs on cardiovascular outcomes in patients with T2D treated with or without SGLT2 inhibitors.
Post hoc analysis of Harmony Outcomes (Albiglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease) evaluating the effect of albiglutide in T2D with cardiovascular disease by background SGLT2 inhibitor use. Additionally, a trial-level meta-analysis of Harmony Outcomes and AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes), which evaluated T2D with cardiovascular or renal disease, was performed, combining the treatment effect estimates according to SGLT2 inhibitor use.
Of the 9,462 participants in Harmony Outcomes, 575 (6.1%) were treated with SGLT2 inhibitors at baseline. The effect of albiglutide on reducing the composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events) was consistent with or without SGLT2 inhibitors (P interaction = 0.70). The effect of albiglutide on secondary outcomes and adverse events was not modified by SGLT2 inhibitors. A meta-analysis of Harmony Outcomes and AMPLITUDE-O included 13,538 patients, of whom 1,193 (8.8%) used SGLT2 inhibitors. Compared to placebo, GLP1-RAs reduced major adverse cardiovascular events without effect modification by SGLT2 inhibitor use (HR: 0.77; 95% CI: 0.68-0.87 without SGLT2 inhibitors; and HR: 0.78; 95% CI: 0.49-1.24 with SGLT2 inhibitors) (P for interaction = 0.95) and reduced heart failure hospitalization (HR: 0.72; 95% CI: 0.55-0.92 vs HR: 0.34; 95% CI: 0.12-0.96) (P for interaction = 0.18).
In patients with T2D and cardiovascular disease, GLP-1 RAs reduced cardiovascular events independently of SGLT2 inhibitor use. These findings suggest that the combination of GLP-1 RAs with SGLT2 inhibitors may further reduce cardiovascular risk. Clinical trials with combination therapy are needed.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂和 GLP-1 受体激动剂（GLP-1 RAs）可降低 2 型糖尿病（T2D）患者的不良心血管结局。然而，联合治疗的疗效尚不清楚。
本研究旨在评估 GLP-1 RAs 在接受或不接受 SGLT2 抑制剂治疗的 T2D 患者中的心血管结局影响。
对 Harmony Outcomes（阿必鲁肽与心血管疾病患者的 2 型糖尿病患者心血管结局）进行事后分析，评估阿必鲁肽在伴有心血管疾病的 T2D 患者中的作用，按背景 SGLT2 抑制剂的使用情况进行分组。此外，还对包含心血管或肾脏疾病的 T2D 患者的 Harmony Outcomes 和 AMPLITUDE-O（Efpeglenatide 对心血管结局的影响）试验进行了荟萃分析，根据 SGLT2 抑制剂的使用情况合并了治疗效果估计值。
在 Harmony Outcomes 中，9462 名参与者中有 575 名（6.1%）基线时接受 SGLT2 抑制剂治疗。阿必鲁肽降低心血管死亡、心肌梗死或卒中（主要不良心血管事件）复合终点的效果与 SGLT2 抑制剂无关（P 交互=0.70）。阿必鲁肽对次要结局和不良事件的影响未被 SGLT2 抑制剂改变。Harmony Outcomes 和 AMPLITUDE-O 的荟萃分析纳入了 13538 名患者，其中 1193 名（8.8%）使用 SGLT2 抑制剂。与安慰剂相比，GLP1-RAs 降低了主要不良心血管事件，但 SGLT2 抑制剂的使用并未改变其效果（HR：0.77；95%CI：0.68-0.87 时无 SGLT2 抑制剂；HR：0.78；95%CI：0.49-1.24 时使用 SGLT2 抑制剂）（P 交互=0.95），并降低了心力衰竭住院率（HR：0.72；95%CI：0.55-0.92 vs HR：0.34；95%CI：0.12-0.96）（P 交互=0.18）。
在伴有心血管疾病的 T2D 患者中，GLP-1 RAs 可降低心血管事件，而不依赖 SGLT2 抑制剂的使用。这些发现表明，GLP-1 RAs 与 SGLT2 抑制剂联合应用可能进一步降低心血管风险。需要进行联合治疗的临床试验。
