tetano
Editor, Senior Moderator
Front Immunol
. 2024 Sep 6:15:1369918.
doi: 10.3389/fimmu.2024.1369918. eCollection 2024. Effect of pioglitazone on inflammatory response and clinical outcome in T2DM patients with COVID-19: a randomized multicenter double-blind clinical trial
Khaled Baagar[SUP] #[/SUP][SUP] 1 [/SUP], Thamer Alessa[SUP] #[/SUP][SUP] 2 [/SUP], Mohamed Abu-Farha[SUP] #[/SUP][SUP] 3 [/SUP], Jehad Abubaker[SUP] 4 [/SUP], Heba Alhumaidi[SUP] 2 [/SUP], Jose Antonio Franco Ceruto[SUP] 1 [/SUP], Mohammad Khair Hamad[SUP] 1 [/SUP], Ali Omrani[SUP] 1 [/SUP], Salma Abdelrahman[SUP] 1 [/SUP], Muhammad Zaka-Ul Haq[SUP] 1 [/SUP], Abdul Wajid Safi[SUP] 1 [/SUP], Bassem Alhariri[SUP] 1 [/SUP], Manish Barman[SUP] 1 [/SUP], Alaaeldin Abdelmajid[SUP] 1 [/SUP], Humberto Vidal Denis Cancio[SUP] 1 [/SUP], Eman Elmekaty[SUP] 5 [/SUP], Irina Al-Khairi[SUP] 4 [/SUP], Preethi Cherian[SUP] 4 [/SUP], Lina Jayyousi[SUP] 6 [/SUP], Mohammed Ahmed[SUP] 3 [/SUP], Mohammed Qaddoumi[SUP] 7 [/SUP], Sulaiman Hajji[SUP] 2 [/SUP], Ahmad Esmaeel[SUP] 2 [/SUP], Ali Al-Andaleeb[SUP] 2 [/SUP], Arshad Channanath[SUP] 8 [/SUP], Sriraman Devarajan[SUP] 8 [/SUP], Hamad Ali[SUP] 8 [/SUP], Thangavel Alphonse Thanaraj[SUP] 8 [/SUP], Salman Al-Sabah[SUP] 2 [/SUP], Fahd Al-Mulla[SUP] 3 [/SUP], Muhammad Abdul-Ghani[SUP] 3 9 [/SUP], Amin Jayyousi[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; inflammation; pioglitazone; type 2 diabetes.
. 2024 Sep 6:15:1369918.
doi: 10.3389/fimmu.2024.1369918. eCollection 2024. Effect of pioglitazone on inflammatory response and clinical outcome in T2DM patients with COVID-19: a randomized multicenter double-blind clinical trial
Khaled Baagar[SUP] #[/SUP][SUP] 1 [/SUP], Thamer Alessa[SUP] #[/SUP][SUP] 2 [/SUP], Mohamed Abu-Farha[SUP] #[/SUP][SUP] 3 [/SUP], Jehad Abubaker[SUP] 4 [/SUP], Heba Alhumaidi[SUP] 2 [/SUP], Jose Antonio Franco Ceruto[SUP] 1 [/SUP], Mohammad Khair Hamad[SUP] 1 [/SUP], Ali Omrani[SUP] 1 [/SUP], Salma Abdelrahman[SUP] 1 [/SUP], Muhammad Zaka-Ul Haq[SUP] 1 [/SUP], Abdul Wajid Safi[SUP] 1 [/SUP], Bassem Alhariri[SUP] 1 [/SUP], Manish Barman[SUP] 1 [/SUP], Alaaeldin Abdelmajid[SUP] 1 [/SUP], Humberto Vidal Denis Cancio[SUP] 1 [/SUP], Eman Elmekaty[SUP] 5 [/SUP], Irina Al-Khairi[SUP] 4 [/SUP], Preethi Cherian[SUP] 4 [/SUP], Lina Jayyousi[SUP] 6 [/SUP], Mohammed Ahmed[SUP] 3 [/SUP], Mohammed Qaddoumi[SUP] 7 [/SUP], Sulaiman Hajji[SUP] 2 [/SUP], Ahmad Esmaeel[SUP] 2 [/SUP], Ali Al-Andaleeb[SUP] 2 [/SUP], Arshad Channanath[SUP] 8 [/SUP], Sriraman Devarajan[SUP] 8 [/SUP], Hamad Ali[SUP] 8 [/SUP], Thangavel Alphonse Thanaraj[SUP] 8 [/SUP], Salman Al-Sabah[SUP] 2 [/SUP], Fahd Al-Mulla[SUP] 3 [/SUP], Muhammad Abdul-Ghani[SUP] 3 9 [/SUP], Amin Jayyousi[SUP] 1 [/SUP]
Affiliations
- PMID: 39308871
- PMCID: PMC11412854
- DOI: 10.3389/fimmu.2024.1369918
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.
Keywords: COVID-19; SARS-CoV-2; inflammation; pioglitazone; type 2 diabetes.