Sodium–glucose co-transporter-2 inhibitors for hospitalised patients with COVID-19: a prospective meta-analysis of randomised trials,The Lancet Diabetes & Endocrinology

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Sodium–glucose co-transporter-2 inhibitors for hospitalised patients with COVID-19: a prospective meta-analysis of randomised trials
The Lancet Diabetes & Endocrinology ( IF 44.0 ) Pub Date : 2024-09-06 , DOI: 10.1016/s2213-8587(24)00219-5
Claire Vale ₁ , Peter J Godolphin ₁ , David Fisher ₁ , Peter W Horby ₂ , Mikhail N Kosiborod ₃ , Judith S Hochman ₄ , Katie Webster ₅ , Julian P T Higgins ₅ , Andrew D Althouse ₆ , Otavio Berwanger ₇ , Remo H M Furtado ₈ , Samvel B Gasparyan ₉ , Richard Haynes ₁₀ , Gary G Koch ₁₁ , Martin Landray ₁₂ , Eric Leifer ₁₃ , John Marshall ₁₄ , Srinivas Murthy ₁₅ , Matthew D Neal ₆ , Natalie Staplin ₁₀ , Janet Diaz ₁₆ , Jonathan A C Sterne ₁₇ , Manu Shankar-Hari ₁₈ ,

Affiliation

MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK.
Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Saint Luke's Mid America Heart Institute, and University of Missouri-Kansas City, Kansas City, MO, USA.
New York University Grossman School of Medicine, New York, NY, USA.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
University of Pittsburgh, Pittsburgh, PA, USA.
George Institute for Global Health UK at Imperial College London, London, UK.
Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Late-stage Development, CVRM, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Clinical Unit, Health Emergencies Programme, World Health Organization, Geneva, Switzerland.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; HDR UK South West, Bristol, UK; NIHR Bristol Biomedical Research Centre, Bristol, UK.
Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.

Background

Sodium–glucose co-transporter-2 (SGLT2) inhibitors have been proposed as a potential treatment for adults hospitalised with COVID-19, due to their potential anti-inflammatory and endothelial protective effects. Published evidence from randomised control trials (RCTs) does not provide evidence of benefit. We aimed to estimate the effect of oral administration of SGLT2 inhibitors compared with usual care or placebo in adults hospitalised with COVID-19.

Methods

Eligible RCTs that estimated the effect of oral administration of SGLT2 inhibitors compared with usual care or placebo on 28-day all-cause mortality (primary outcome) were included in this prospective meta-analysis. The primary safety outcome was ketoacidosis by 28 days. Trials were identified through systematic searches of ClinicalTrials.gov, EudraCT, and the WHO ISRCTN registry between Nov 1, 2022 and Jan 31, 2023. The search terms were “random*” AND “COVID” AND each SGLT2i, not restricted by trial status or language. Individual searches were then combined. Prespecified summary outcome data, overall and within subgroups of interest, were provided by each trial. The primary analyses were inverse variance weighted meta-analysis of odds ratios (ORs). Risk of bias was assessed using the Cochrane Risk of Bias tool. This study was registered with PROSPERO, CRD42023406442.

Findings

Three eligible trials randomly assigned 6096 participants (3025 to the SGLT2 inhibitor group and 3071 to the usual care or placebo group). 2381 (39%) patients were women and 1547 (25%) had type 2 diabetes at randomisation. By 28 days, there were 351 deaths in the SGLT2 inhibitor group and 382 deaths in the usual care or placebo group (summary OR 0·93 [95% CI 0·79–1·08]; p=0·33, I² for inconsistency across trials 0%). The risk of bias was assessed as being low. Ketoacidosis was observed in seven participants in the SGLT2 inhibitor group and two patients in the usual care or placebo group.

Interpretation

Although administration of SGLT2 inhibitor was safe, we found no clear evidence that adding SGLT2 inhibitor therapy improved outcomes in patients hospitalised with COVID-19 compared with usual care or placebo. These data do not support the use of SGLT2 inhibitors as standard treatment in adults hospitalised for COVID-19.

Funding

None.

中文翻译：

钠-葡萄糖协同转运蛋白 2 抑制剂治疗 COVID-19 住院患者：随机试验的前瞻性荟萃分析

背景

钠-葡萄糖协同转运蛋白 2 （SGLT2）抑制剂因其潜在的抗炎和内皮保护作用而被提议作为 COVID-19 住院成人的潜在治疗方法。来自随机对照试验（RCT）的已发表证据并未提供获益证据。我们旨在评估口服 SGLT2 抑制剂与常规护理或安慰剂相比对 COVID-19 住院成人的影响。

方法

本前瞻性荟萃分析纳入了评估口服 SGLT2 抑制剂与常规护理或安慰剂相比对 28 天全因死亡率（主要结局）影响的合格 RCT。主要安全性结局是 28 天时的酮症酸中毒。在 2022 年 11 月 1 日至 2023 年 1 月 31 日期间，通过对 ClinicalTrials.gov、EudraCT 和 WHO ISRCTN 注册库进行系统检索来确定试验。检索词是 “random*” 和 “COVID” 以及每个 SGLT2i，不受试验状态或语言的限制。然后合并个体检索。每项试验都提供了预先指定的汇总结局数据，包括总体和感兴趣的亚组。主要分析是比值比（ORs）的逆方差加权荟萃分析。使用 Cochrane 偏倚风险工具评估偏倚风险。这项研究已在 CRD42023406442 年 PROSPERO 注册。

发现

三项符合条件的试验随机分配了 6096 名受试者（3025 名被分配到 SGLT2 抑制剂组，3071 名被分配到常规护理或安慰剂组）。随机分组时，2381 名（39%）患者为女性，1547 名（25%）患有 2 型糖尿病。到 28 天时，SGLT2 抑制剂组有 351 例死亡，常规护理或安慰剂组有 382 例死亡（总 OR 0·93 [95% CI 0·79–1·08];p=0·33，I ² 试验之间的不一致性 0%）。偏倚风险被评估为低。在 SGLT2 抑制剂组的 7 名参与者和常规护理或安慰剂组的 2 名患者中观察到酮症酸中毒。