Abdel Jawad Mohammad, Furtado Remo H M, Esterline Russell, Oscarsson Jan, Gasparyan Samvel B, Koch Gary G, Martinez Felipe, Mukhtar Omar, Verma Subodh, Langkilde Anna Maria, Ambery Philip, Patel Shachi, Gosch Kensey, Windsor Sheryl L, Soares Ronaldo V P, Moia Diogo D F, Aboudara Matthew, Javaheri Ali, Saraiva J F Kerr, Maia Lilia Nigro, Berwanger Otavio, Sauer Andrew J, Kosiborod Mikhail N
Saint Luke's Mid America Heart Institute, Kansas City, MO, USA.
University of Missouri-Kansas City, Kansas City, MO, USA.
Cardiovasc Diabetol. 2025 Jul 30;24(1):307. doi: 10.1186/s12933-025-02875-6.
Although several previous studies tested SGLT2 inhibitors in the setting of an acute, non-cardiovascular illness, detailed information on their efficacy and safety among participants with and without type 2 diabetes (T2D) from double-blind randomized trials is lacking. In this secondary prespecified analysis of the Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial, we sought to evaluate the safety and efficacy of initiating dapagliflozin during acute illness with COVID-19 in patients with and without T2D.
The DARE-19 trial randomized 1250 patients hospitalized with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. T2D was present in 636/1250 (50.9%) of the cohort. Dual primary outcomes were evaluated: prevention (time to new or worsened organ dysfunction or death) and a hierarchical composite outcome of recovery (change in clinical status by day 30). Key biomarkers (serum bicarbonate, estimated glomerular filtration rate [eGFR], hematocrit, and glucose) and safety were assessed in participants with and without T2D during index hospitalization.
Among patients with T2D, the prevention outcome occurred in 10.9% receiving dapagliflozin versus 13.9% receiving placebo (hazard ratio [HR] 0.76, 95% CI 0.49-1.18). In patients without diabetes, the event rate was 11.5% with dapagliflozin versus 13.3% with placebo (HR 0.86, 95% CI 0.55-1.35; interaction p = 0.668). For the primary recovery outcome, no significant differences were observed between dapagliflozin and placebo groups regardless of diabetes status (interaction p = 0.222). Close laboratory monitoring revealed similarities in serum bicarbonate, eGFR, or hematocrit for the dapagliflozin and placebo groups, irrespective of T2D status. Any serious adverse event was reported in 12·7% of patients in the dapagliflozin group, 14·3% in the placebo group among patients with T2D, and in 8·5% of patients in the dapagliflozin group, and 11·9% in the placebo group in patients without T2D. Diabetes ketoacidosis was reported in two patients with T2D in the dapagliflozin group.
Initiating dapagliflozin in patients hospitalized for acute COVID-19 was well tolerated and safe, irrespective of T2D status. Serum biomarker levels remained stable and comparable between treatment groups, indicating no increased risk of adverse metabolic or renal effects with dapagliflozin in this clinical scenario.
The trial was registered on ClinicalTrials.gov (NCT04350593).
尽管先前有多项研究在急性非心血管疾病背景下对钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂进行了测试，但缺乏来自双盲随机试验的关于其在2型糖尿病（T2D）患者和非T2D患者中疗效和安全性的详细信息。在这项对达格列净治疗2019冠状病毒病（COVID-19）患者呼吸衰竭（DARE-19）试验的二次预先设定分析中，我们试图评估在COVID-19急性病期间开始使用达格列净治疗T2D患者和非T2D患者的安全性和疗效。
DARE-19试验将1250例因COVID-19住院且有心脏代谢危险因素的患者随机分为达格列净组或安慰剂组。该队列中636/1250（50.9%）的患者患有T2D。评估了两个主要结局：预防（出现新的或恶化的器官功能障碍或死亡的时间）和恢复的分层综合结局（第30天时临床状态的变化）。在住院期间对有或无T2D的参与者评估了关键生物标志物（血清碳酸氢盐、估计肾小球滤过率[eGFR]、血细胞比容和血糖）及安全性。
在T2D患者中，接受达格列净治疗的患者预防结局发生率为10.9%，接受安慰剂治疗的患者为13.9%（风险比[HR]0.76，95%置信区间[CI]0.49 - 1.18）。在无糖尿病患者中，达格列净组的事件发生率为11.5%，安慰剂组为13.3%（HR 0.86，95%CI 0.55 - 1.35；交互作用p = 0.668）。对于主要的恢复结局，无论糖尿病状态如何，达格列净组和安慰剂组之间均未观察到显著差异（交互作用p = 0.222）。严密的实验室监测显示，无论T2D状态如何，达格列净组和安慰剂组的血清碳酸氢盐、eGFR或血细胞比容相似。达格列净组12.7%的患者、T2D患者中安慰剂组14.3%的患者、非T2D患者中达格列净组8.5%的患者以及安慰剂组11.9%的患者报告了任何严重不良事件。达格列净组有两名T2D患者报告了糖尿病酮症酸中毒。
对于因急性COVID-19住院的患者，无论T2D状态如何，开始使用达格列净耐受性良好且安全。治疗组之间血清生物标志物水平保持稳定且相当，表明在此临床场景下达格列净不会增加不良代谢或肾脏影响风险。
该试验已在ClinicalTrials.gov上注册（NCT04350593）。
