A Randomized Trial of Sitagliptin and Spironolactone With Combination Therapy in Hospitalized Adults With COVID-19
Farhad Abbasi, Reuben Adatorwovor, Mohammad Ali Davarpanah, Yasaman Mansoori, Mehdi Hajiani, Farzan Azodi, Sepideh Sefidbakht, Shayesteh Davoudi, Farzana Rezaei, Shayan Mohammadmoradi, MD Kamyar Asadipooya
Journal of the Endocrine Society, doi:10.1210/jendso/bvac017
Context: COVID-19 may cause respiratory distress syndrome and death. Treatment of COVID-19 to prevent complications remains a priority. Objective: Our investigation sought to determine whether combination of spironolactone and sitagliptin could reduce mortality for inpatients with SARS-CoV-2 infection. Methods: This single-blind, 4-arm, prospective randomized clinical trial was conducted at Shiraz and Bushehr University of Medical Sciences hospitals between December 2020 and April 2021. We randomized hospitalized adult patients with COVID-19 pneumonia into 4 groups: control, combination therapy, sitagliptin add-on, or spironolactone add-on. The primary outcome was the clinical improvement of the patients in the hospital as measured on an 8-point numerical scale. The secondary outcomes included intubation, ICU admission, end organ damages, CT findings, and paraclinical information. Results: A total of 263 admitted patients were randomly assigned to control group (87 patients), combination group (60 patients), sitagliptin group (66 patients), and spironolactone group (50 patients). There were no significant differences in baseline characteristics, except for higher age in control group. The intervention groups, especially combination therapy, had better clinical outcomes (clinical score on fifth day of admission: 3.11 ± 2.45 for controls, 1.33 ± 0.50 for combination, 1.68 ± 1.02 for sitagliptin, and 1.64 ± 0.81 for spironolactone; P = 0.004). However, the mortality rate was lower in patients who received spironolactone (21.84% control, 13.33% combination, 13.64% sitagliptin, 10.00% spironolactone; P = 0.275). Our intervention reduced lung infiltration but not the area of involvement in lungs. Conclusion: Sitagliptin and spironolactone can potentially improve clinical outcomes of hospitalized COVID-19 patients.
Abbreviations: CT, computed tomography; ECMO, extracorporeal membrane oxygenation; PCR, polymerase chain reaction.
Financial Support This project is supported by Vice-Chancellor for Research at the Shiraz University of Medical Sciences, Bushehr University Medical Sciences, Faghihi Hospital and Shohadaye_Khalije_ Fars Hospital.
Author Contributions Kamyar Asadipooya proposed the idea, designed the study, and wrote the manuscript. Farhad Abbasi and Mohammad Ali Davarpanah helped designi the study. Reuben Adatorwovor provided statistical analysis, wrote the statistical portions, and revised the manuscript. Sepideh Sefidbakht and Farhad abbasi read the CT scan results. Yasaman Mansoori, Mehdi Hajiani, Farzan Azodi, Shayesteh Davoudi, and Farzana Rezaei collected the data. Shayan Mohammadmoradi helped with designing the study and editing the manuscript. All authors approved the final version of the manuscript.
Disclosures The authors have declared that no conflict of interest exists.
Iranian Registry of Clinical Trial Information Iranian Registry of Clinical Trial registration number: IRCT20201003048904N2; registration date: December 10, 2020.
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