Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2024

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2024.1369918

PMID

39308871

PMCID

PMC11412854

PubMedCentral® Posted Date

9-6-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Background: 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.

Method: 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 (n = 189) or a matching placebo (n = 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.

Results: 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], p = 0.043 vs. 2.28 (± 1.67) [95% CI: - 0.23, 0.86], p = 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.

Conclusion: 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.

Keywords

Humans, Pioglitazone, Diabetes Mellitus, Type 2, Male, Female, Middle Aged, Double-Blind Method, COVID-19, COVID-19 Drug Treatment, SARS-CoV-2, Hypoglycemic Agents, Treatment Outcome, Aged, C-Reactive Protein, Qatar, Inflammation, Adult, Kuwait, COVID-19, SARS-CoV-2, inflammation, type 2 diabetes, pioglitazone

Comments

Clinical trial registration: https://clinicaltrials.gov, identifier NCT04604223.

Published Open-Access

yes

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