TY - JOUR
T1 - Effect of pioglitazone on inflammatory response and clinical outcome in T2DM patients with COVID-19
T2 - a randomized multicenter double-blind clinical trial
AU - Baagar, Khaled
AU - Alessa, Thamer
AU - Abu-Farha, Mohamed
AU - Abubaker, Jehad
AU - Alhumaidi, Heba
AU - Franco Ceruto, Jose Antonio
AU - Hamad, Mohammad Khair
AU - Omrani, Ali
AU - Abdelrahman, Salma
AU - Zaka-Ul Haq, Muhammad
AU - Safi, Abdul Wajid
AU - Alhariri, Bassem
AU - Barman, Manish
AU - Abdelmajid, Alaaeldin
AU - Cancio, Humberto Vidal Denis
AU - Elmekaty, Eman
AU - Al-Khairi, Irina
AU - Cherian, Preethi
AU - Jayyousi, Lina
AU - Ahmed, Mohammed
AU - Qaddoumi, Mohammed
AU - Hajji, Sulaiman
AU - Esmaeel, Ahmad
AU - Al-Andaleeb, Ali
AU - Channanath, Arshad
AU - Devarajan, Sriraman
AU - Ali, Hamad
AU - Thanaraj, Thangavel Alphonse
AU - Al-Sabah, Salman
AU - Al-Mulla, Fahd
AU - Abdul-Ghani, Muhammad
AU - Jayyousi, Amin
N1 - Publisher Copyright:
Copyright © 2024 Baagar, Alessa, Abu-Farha, Abubaker, Alhumaidi, Franco Ceruto, Hamad, Omrani, Abdelrahman, Zaka-Ul Haq, Safi, Alhariri, Barman, Abdelmajid, Cancio, Elmekaty, Al-Khairi, Cherian, Jayyousi, Ahmed, Qaddoumi, Hajji, Esmaeel, Al-Andaleeb, Channanath, Devarajan, Ali, Thanaraj, Al-Sabah, Al-Mulla, Abdul-Ghani and Jayyousi.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - COVID-19
KW - SARS-CoV-2
KW - inflammation
KW - pioglitazone
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85204722003&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2024.1369918
DO - 10.3389/fimmu.2024.1369918
M3 - Article
C2 - 39308871
AN - SCOPUS:85204722003
SN - 1664-3224
VL - 15
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1369918
ER -
