Medicine Department, Hamad Medical Corporation, Doha, Qatar.
Jaber AlAhmed Hospital, Ministry of Health, Kuwait City, Kuwait.
Front Immunol. 2024 Sep 6;15:1369918. doi: 10.3389/fimmu.2024.1369918. eCollection 2024.
Coronavirus disease 2019 (COVID-19) caused by the coronavirus SARS-CoV-2, has emerged as a rapidly spreading contagious disease across the globe. Recent studies showed that people with diabetes mellitus, severe obesity, and cardiovascular disease are at higher risk of mortality from COVID-19. It has been suggested that the increased risk is due to the chronic inflammatory state associated with type 2 diabetes. This study aimed to evaluate the efficacy of pioglitazone, a strong insulin sensitizer with anti-inflammatory properties, in improving the clinical outcomes of patients with type 2 diabetes admitted with moderate-severe COVID-19.
We enrolled 350 patients with type 2 diabetes who were admitted to hospitals in Qatar and Kuwait with COVID-19. Patients were randomized to receive, in a double-blind fashion, pioglitazone ( = 189) or a matching placebo ( = 161) for 28 days. The study had two primary outcomes: (1) the incidence of a composite outcome composed of (a) the requirement for mechanical ventilation, (b) death, and (c) myocardial damage; and (2) an increase in C-reactive protein (CRP) levels.
The first primary outcome occurred in 28 participants (8%), and the secondary outcome occurred in 17. Treatment with pioglitazone showed a significant reduction in interleukin (IL)-3 levels compared with placebo treatment (mean (SD) 2.73 (± 2.14) [95% CI: 0.02, 1.1], = 0.043 vs. 2.28 (± 1.67) [95% CI: - 0.23, 0.86], = 0.3, respectively), with no effect seen in the levels of other inflammatory markers. Even though not significant, a few of the patients on pioglitazone exhibited serum troponin levels > 3 times higher than the normal range seen in patients on placebo. On the other hand, more patients on pioglitazone were admitted to the ICU than those with placebo, and no significant difference in the CRP reduction was observed between the two groups.
The results of the present study demonstrate that pioglitazone treatment did not independently provide any additional clinical benefit to patients with type 2 diabetes admitted with a COVID-19 infection.
https://clinicaltrials.gov, identifier NCT04604223.
由冠状病毒 SARS-CoV-2 引起的 2019 年冠状病毒病（COVID-19）已在全球迅速传播。最近的研究表明，糖尿病、严重肥胖和心血管疾病患者因 COVID-19 而死亡的风险更高。有人认为，这种风险增加是由于 2 型糖尿病相关的慢性炎症状态。本研究旨在评估吡格列酮的疗效，吡格列酮是一种具有抗炎特性的强胰岛素增敏剂，可改善中重度 COVID-19 住院的 2 型糖尿病患者的临床结局。
我们招募了 350 名在卡塔尔和科威特的医院因 COVID-19 住院的 2 型糖尿病患者。患者以双盲方式随机接受吡格列酮（=189）或匹配安慰剂（=161）治疗 28 天。该研究有两个主要结局：（1）由（a）需要机械通气、（b）死亡和（c）心肌损伤组成的复合结局的发生率；（2）C 反应蛋白（CRP）水平升高。
28 名参与者（8%）发生了第一个主要结局，17 名参与者发生了次要结局。与安慰剂治疗相比，吡格列酮治疗显著降低了白细胞介素（IL）-3 水平（平均值（标准差）2.73（±2.14）[95%CI：0.02，1.1]，=0.043 与 2.28（±1.67）[95%CI：-0.23，0.86]，=0.3，分别），而其他炎症标志物水平没有影响。尽管没有统计学意义，但少数服用吡格列酮的患者的肌钙蛋白血清水平比服用安慰剂的患者高出正常值的 3 倍以上。另一方面，与服用安慰剂的患者相比，服用吡格列酮的患者有更多的人被收入 ICU，但两组之间 CRP 降低无显著差异。
本研究结果表明，吡格列酮治疗并不能为 COVID-19 感染住院的 2 型糖尿病患者提供任何额外的临床益处。
临床试验.gov，标识符 NCT04604223。
