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

Abstract

Background COVID-19 may cause respiratory distress syndrome and death. Treatment of COVID-19 to prevent complications remains a priority. Our investigation sought to determine whether combination of spironolactone and sitagliptin could reduce mortality for inpatient with SARS-CoV-2 infection. Methods This single blind, 4-arms, 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 four 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 eight-point numerical scale. The secondary outcomes included intubation, ICU admission, end organ damages, CT findings and paraclinical information. Results 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 5th day of admission was 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; with p-value = 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-value = 0.275). Our intervention reduced lung infiltration but not the area of involvement in lung. Conclusion Sitagliptin and spironolactone can potentially improve clinical outcomes of hospitalized COVID-19 patients.

Combination of Spironolactone and Sitagliptin Improves Clinical Outcomes of Outpatients with COVID-19: A Prospective Cohort Study

“…The proposed mechanisms could be the immunomodulatory functions (29), reduction of virus entry and diminishing viral replication. Therefore, the combination of DPP4 inhibitors and spironolactone could potentially improve the clinical outcomes better than each one alone (36).…”

“…The Institutional Review Boards of the University of Kentucky, and Shiraz University of Medical Sciences approved the study. The current trial is registered as an addendum to the previous trial, which was conducted on the admitted patients (36). The authors confirm that all ongoing and related trials for these drugs are registered.…”

Integrative analysis of viral entry networks and clinical outcomes identifies a protective role for spironolactone in severe COVID-19

“…Despite a variety of mechanistic hypotheses, few investigations of either clinical efficacy or in vitro effect have been performed for spironolactone in COVID-19. A recent interventional study of spironolactone-sitagliptin combination therapy showed statistically non-significant improvements in clinical outcomes, including mortality, ICU admission, intubation rate, and end-organ damage, for patients on spironolactone (44). Another interventional trial showed no significant clinical improvements for COVID-19 patients on potassium canrenoate, a mineralocorticoid receptor antagonist similar to spironolactone (45).…”

Biochemical Investigation of Therapeutic Potentials of Plant-Based Bioactive Compounds as Stimulators of Glucagon like peptide-1 Secretion

“…Interestingly, many recent studies have investigated the antioxidant and anti-inflammatory effects of these inhibitors. 6 - 13 …”