GLP-1 Receptor Agonist Therapy With and Without SGLT2 Inhibitors in Patients With Type 2 Diabetes,Journal of the American College of Cardiology

当前位置： X-MOL 学术 › J. Am. Coll. Cardiol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

GLP-1 Receptor Agonist Therapy With and Without SGLT2 Inhibitors in Patients With Type 2 Diabetes
Journal of the American College of Cardiology ( IF 21.7 ) Pub Date : 2023-07-31 , DOI: 10.1016/j.jacc.2023.05.048
João Sérgio Neves ₁ , Marta Borges-Canha ₁ , Francisco Vasques-Nóvoa ₂ , Jennifer B Green ₃ , Lawrence A Leiter ₄ , Christopher B Granger ₃ , Davide Carvalho ₅ , Adelino Leite-Moreira ₆ , Adrian F Hernandez ₃ , Stefano Del Prato ₇ , John J V McMurray ₈ , João Pedro Ferreira ₉

Affiliation

Cardiovascular R&D 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 Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal; Department of Internal Medicine, Centro Hospitalar Universitário de São João, Porto, Portugal.
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine of the University of Porto, Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Cardiovascular R&D Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal; Department of Cardiothoracic Surgery, Centro Hospitalar Universitário São João, Porto, Portugal.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Cardiovascular R&D Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal; Université de Lorraine, Inserm, Centre d'Investigations Cliniques Plurithématique 14-33, and Inserm U1116, CHRU Nancy, Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.

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 ( 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) ( 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) ( 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.

中文翻译：

2 型糖尿病患者联合或不联合 SGLT2 抑制剂的 GLP-1 受体激动剂治疗

钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂和 GLP-1 受体激动剂 (GLP-1 RA) 可减少 2 型糖尿病 (T2D) 的不良心血管结局。然而，联合治疗的疗效尚不清楚。本研究的目的是评估 GLP-1 RA 对接受或不接受 SGLT2 抑制剂治疗的 T2D 患者心血管结局的影响。 Harmony 结果（2 型糖尿病和心血管疾病患者的阿必鲁肽和心血管结果）的事后分析通过背景 SGLT2 抑制剂的使用评估了阿必鲁肽对患有心血管疾病的 T2D 的影响。此外，还对 Harmony Outcomes 和 AMPLITUDE-O（Efpeglenatide 对心血管结果的影响）进行了试验级荟萃分析，评估了患有心血管或肾脏疾病的 T2D，并结合了根据 SGLT2 抑制剂使用的治疗效果估计。 Harmony Outcomes 的 9,462 名参与者中，有 575 名 (6.1%) 在基线时接受了 SGLT2 抑制剂治疗。无论是否使用 SGLT2 抑制剂，阿必鲁肽对减少心血管死亡、心肌梗塞或中风（主要不良心血管事件）的复合效应均一致（相互作用 = 0.70）。 SGLT2 抑制剂不会改变阿必鲁肽对次要结局和不良事件的影响。 Harmony Outcomes 和 AMPLITUDE-O 的荟萃分析包括 13,538 名患者，其中 1,193 名 (8.8%) 使用 SGLT2 抑制剂。与安慰剂相比，GLP1-RA 减少了主要不良心血管事件，且未因使用 SGLT2 抑制剂而改变效果（不使用 SGLT2 抑制剂时，HR：0.77；95% CI：0.68-0.87；使用 SGLT2 抑制剂时，HR：0.78；95% CI：0.49-1.24））（交互作用 = 0.95）并减少心力衰竭住院率（HR：0.72；95% CI：0.55-0.92 vs HR：0.34；95% CI：0。12-0.96)（交互=0.18）。在患有 T2D 和心血管疾病的患者中，GLP-1 RA 可以减少心血管事件，而与 SGLT2 抑制剂的使用无关。这些发现表明，GLP-1 RA 与 SGLT2 抑制剂的组合可能会进一步降低心血管风险。需要联合治疗的临床试验。

更新日期：2023-07-31

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南