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; Kamyar Asadipooya

doi:10.1210/jendso/bvac017

A Randomized Trial of Sitagliptin and Spironolactone With Combination Therapy in Hospitalized Adults With COVID-19

J Endocr Soc. 2022 Feb 7;6(4):bvac017. doi: 10.1210/jendso/bvac017. eCollection 2022 Apr 1.

Authors

Affiliations

¹ Department of Infectious Diseases, Bushehr University of Medical Sciences, Bushehr 75179-33755, Iran.
² Department of Biostatistics, University of Kentucky, Lexington, KY 40536,USA.
³ Shiraz HIV/AIDS Research Center, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran.
⁴ Student Research Committee, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran.
⁵ Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr 75179-33755, Iran.
⁶ Medical Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran.
⁷ Student Research Committee, Bushehr University of Medical Sciences, Bushehr 75179-33755, Iran.
⁸ Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536, USA.
⁹ Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536,USA.
¹⁰ Assistant Professor of Medicine, Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, KY 40504, USA.

Abstract

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.

Keywords: ACE2; COVID-19; DPP4 inhibitor; spironolactone.