AUTHOR=Baagar Khaled , Alessa Thamer , Abu-Farha Mohamed , Abubaker Jehad , Alhumaidi Heba , Franco Ceruto Jose Antonio , Hamad Mohammad Khair , Omrani Ali , Abdelrahman Salma , Zaka-Ul Haq Muhammad , Safi Abdul Wajid , Alhariri Bassem , Barman Manish , Abdelmajid Alaaeldin , Cancio Humberto Vidal Denis , Elmekaty Eman , Al-Khairi Irina , Cherian Preethi , Jayyousi Lina , Ahmed Mohammed , Qaddoumi Mohammed , Hajji Sulaiman , Esmaeel Ahmad , Al-Andaleeb Ali , Channanath Arshad , Devarajan Sriraman , Ali Hamad , Thanaraj Thangavel Alphonse , Al-Sabah Salman , Al-Mulla Fahd , Abdul-Ghani Muhammad , Jayyousi Amin TITLE=Effect of pioglitazone on inflammatory response and clinical outcome in T2DM patients with COVID-19: a randomized multicenter double-blind clinical trial JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1369918 DOI=10.3389/fimmu.2024.1369918 ISSN=1664-3224 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.

Clinical trial registration

https://clinicaltrials.gov, identifier NCT04604223.