Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials,The Lancet Diabetes & Endocrinology

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Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials
The Lancet Diabetes & Endocrinology ( IF 44.0 ) Pub Date : 2024-07-08 , DOI: 10.1016/s2213-8587(24)00155-4
Ellen M Apperloo ₁ , Brendon L Neuen ₂ , Robert A Fletcher ₃ , Niels Jongs ₁ , Stefan D Anker ₄ , Deepak L Bhatt ₅ , Javed Butler ₆ , David Z I Cherney ₇ , William G Herrington ₈ , Silvio E Inzucchi ₉ , Meg J Jardine ₁₀ , Chih-Chin Liu ₁₁ , Kenneth W Mahaffey ₁₂ , Darren K McGuire ₁₃ , John J V McMurray ₁₄ , Bruce Neal ₁₅ , Milton Packer ₁₆ , Vlado Perkovic ₃ , Marc S Sabatine ₁₇ , Scott D Solomon ₁₈ , Natalie Staplin ₈ , Michael Szarek ₁₉ , Muthiah Vaduganathan ₁₈ , Christoph Wanner ₂₀ , David C Wheeler ₂₁ , Stephen D Wiviott ₁₇ , Faiez Zannad ₂₂ , Hiddo J L Heerspink ₂₃

Affiliation

Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Department of Renal Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.
The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Department of Cardiology and Berlin Institute of Health Center for Regenerative Therapies, German Center for Cardiovascular Research Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.
Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Baylor Scott and White Research Institute, Dallas, TX, USA; Department of Medicine, University of Mississippi School of Medicine, Jackson, MS, USA.
Department of Medicine, Division of Nephrology, Toronto General Hospital, ON, Canada.
Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Section of Endocrinology, Yale School of Medicine, New Haven, CT, USA.
The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia; Department of Renal Medicine, Concord Repatriation General Hospital, Sydney, NSW, Australia.
Merck, Rahway, NJ, USA.
Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
University of Texas Southwestern Medical Center and Parkland Health, Dallas, TX, USA.
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
Baylor University Medical Center, Dallas TX, USA; Imperial College, London, UK.
TIMI Study Group, Boston, MA, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA; Colorado Prevention Center Clinical Research, Aurora, CO, USA; State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA.
Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Centre, University Hospital, Würzburg, Germany.
Department of Renal Medicine, University College London, London, UK.
Université de Lorraine, Inserm, Center d'Investigations Cliniques, Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.

SGLT2 inhibitors and GLP-1 receptor agonists both improve cardiovascular and kidney outcomes in patients with type 2 diabetes. We sought to evaluate whether the benefits of SGLT2 inhibitors are consistent in patients receiving and not receiving GLP-1 receptor agonists. We conducted a collaborative meta-analysis of trials included in the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium, restricted to participants with diabetes. Treatment effects from individual trials were obtained from Cox regression models and pooled using inverse variance weighted meta-analysis. The two main cardiovascular outcomes assessed included major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), and hospitalisation for heart failure or cardiovascular death. The main kidney outcomes assessed were chronic kidney disease progression (≥40% decline in estimated glomerular filtration rate [eGFR], kidney failure [eGFR <15 mL/min/1·73 m, chronic dialysis, or kidney transplantation], or death due to kidney failure), and the rate of change in eGFR over time. Safety outcomes were also assessed. Across 12 randomised, double-blind, placebo-controlled trials, 3065 (4·2%) of 73 238 participants with diabetes were using GLP-1 receptor agonists at baseline. SGLT2 inhibitors reduced the risk of major adverse cardiovascular events in participants both receiving and not receiving GLP-1 receptor agonists (hazard ratio [HR] 0·81, 95% CI 0·63–1·03 0·90, 0·86–0·94; p-heterogeneity=0·31). Effects on hospitalisation for heart failure or cardiovascular death (0·76, 0·57–1·01 0·78, 0·74–0·82; p-heterogeneity=0·90) and chronic kidney disease progression (0·65, 0·46–0·94 0·67, 0·62–0·72; p-heterogeneity=0·81) were also consistent regardless of GLP-1 receptor agonist use, as was the effect on the chronic rate of change in eGFR over time (heterogeneity=0·92). Fewer serious adverse events occurred with SGLT2 inhibitors compared with placebo, irrespective of GLP-1 receptor agonist use (relative risk 0·87, 95% CI 0·79–0·96 0·91, 0·89–0·93; p-heterogeneity=0·41). The effects of SGLT2 inhibitors on cardiovascular and kidney outcomes are consistent regardless of the background use of GLP-1 receptor agonists. These findings suggest independent effects of these evidence-based therapies and support clinical practice guidelines recommending the use of these agents in combination to improve cardiovascular and kidney metabolic outcomes. National Health and Medical Research Council of Australia and the Ramaciotti Foundation.

中文翻译：

SGLT2 抑制剂联合和联合胰高血糖素样肽 1 受体激动剂的疗效和安全性：随机对照试验的 SMART-C 合作荟萃分析

SGLT2 抑制剂和 GLP-1 受体激动剂均可改善 2 型糖尿病患者的心血管和肾脏预后。我们试图评估 SGLT2 抑制剂在接受和未接受 GLP-1 受体激动剂患者中的益处是否一致。我们对SGLT2抑制剂荟萃分析心肾试验者联盟（Cardio-Renal Trialists' Consortium）中纳入的试验进行了合作meta分析，仅限于糖尿病受试者。从 Cox 回归模型获得个体试验的治疗效果，并使用逆方差加权荟萃分析进行合并。评估的两种主要心血管结局包括主要不良心血管事件（非致命性心肌梗死、非致命性卒中或心血管死亡）和因心力衰竭或心血管死亡而住院。评估的主要肾脏结局是慢性肾病进展（估计肾小球滤过率 [eGFR] 下降 ≥40%）、肾功能衰竭 [eGFR <15 mL/min/1·73 m、慢性透析或肾移植]或肾功能衰竭导致的死亡）和 eGFR 随时间的变化率。还评估了安全性结局。在 12 项随机、双盲、安慰剂对照试验中，73 238 名糖尿病参与者中有 3065 名（4·2%）在基线时使用 GLP-1 受体激动剂。SGLT2 抑制剂降低了接受和未接受 GLP-1 受体激动剂的参与者发生主要不良心血管事件的风险（风险比 [HR] 0·81,95% CI 0·63–1·03 0·90,0·86–0·94;p-异质性=0·31）。对心力衰竭或心血管死亡住院治疗（0·76， 0·57–1·01 0·78， 0·74–0·82;p-异质性 = 0·90）和慢性肾病进展（0·65， 0·46–0·94 0·67， 0·62–0·72;p-异质性 = 0·81）的影响也一致，无论是否使用 GLP-1 受体激动剂，对 eGFR 慢性变化率随时间变化率的影响也是一致的（异质性 = 0·92）。与安慰剂相比，无论是否使用 GLP-1 受体激动剂，SGLT2 抑制剂的严重不良事件发生率均较低（相对风险 0·87,95% CI 0·79–0·96 0·91,0·89–0·93;p-异质性=0·41）。无论 GLP-1 受体激动剂的背景使用如何，SGLT2 抑制剂对心血管和肾脏结局的影响都是一致的。这些发现表明这些循证疗法的独立作用，并支持推荐联合使用这些药物以改善心血管和肾脏代谢结局的临床实践指南。澳大利亚国家健康与医学研究委员会和 Ramaciotti 基金会。

更新日期：2024-07-08

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