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Combination of spironolactone and sitagliptin improves clinical outcomes of outpatients with COVID-19: a prospective cohort study

Davarpanah et al., Journal of Endocrinological Investigation, doi:10.1007/s40618-023-02141-0 (date from preprint)
Jan 2022  
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Hospitalization 78% Improvement Relative Risk ER visit 67% Recovery time 64% Spironolactone  Davarpanah et al.  LATE TREATMENT Is late treatment with spironolactone + sitagliptin beneficial for COVID-19? Prospective study of 206 patients in Iran (July - September 2021) Lower hospitalization (p=0.0008) and progression (p=0.0034) c19early.org Davarpanah et al., J. Endocrinological.., Jan 2022 Favorsspironolactone Favorscontrol 0 0.5 1 1.5 2+
33rd treatment shown to reduce risk in February 2022, now with p = 0.00046 from 12 studies.
Lower risk for mortality, progression, and recovery.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19early.org
Prospective study of 206 outpatients in Iran, 103 treated with spironolactone and sitagliptin, showing lower hospitalization and faster recovery with treatment. spironolactone 100mg and sitagliptin 100mg daily.
risk of hospitalization, 78.3% lower, RR 0.22, p < 0.001, treatment 6 of 103 (5.8%), control 23 of 103 (22.3%), NNT 6.1, adjusted per study, odds ratio converted to relative risk, multivariable.
ER visit, 66.7% lower, RR 0.33, p = 0.003, treatment 8 of 103 (7.8%), control 24 of 103 (23.3%), NNT 6.4.
recovery time, 64.4% lower, relative time 0.36, p < 0.001, treatment 103, control 103.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Davarpanah et al., 21 Jan 2022, prospective, Iran, peer-reviewed, 9 authors, study period July 2021 - September 2021, average treatment delay 5.74 days, this trial uses multiple treatments in the treatment arm (combined with sitagliptin) - results of individual treatments may vary.
This PaperSpironolactoneAll
Combination of Spironolactone and Sitagliptin Improves Clinical Outcomes of Outpatients with COVID-19: A Prospective Cohort Study
Mohammad Ali Davarpanah, Reuben Adatorwovor, Yasaman Mansoori, Fatemeh Sadat Rajaie Ramsheh, Amir Parsa, Mehdi Hajiani, Hossein Faramarzi, Ramakanth Kavuluru, MD Kamyar Asadipooya
doi:10.1101/2022.01.21.22269322
Background: Coronavirus disease 2019 (COVID-19) leads to hospitalization and death, especially in elderly and those with comorbidities. There are evidences showing that sitagliptin and spironolactone can potentially improve the clinical outcomes of COVID-19 cases. In this observational study on acutely symptomatic outpatient COVID-19 cases, we investigated the effects of spironolactone and sitagliptin on the outcomes of the disease. Methods: This prospective cohort study was conducted at Shiraz University of Medical Sciences Clinics during the fifth wave of the COVID-19 pandemic between July 2021 and September 2021. We followed mild to moderate symptomatic COVID-19 patients, who were treated with either combination (spironolactone 100 mg daily and sitagliptin 100 mg daily) or standard (steroid, antiviral and/or supportive care) therapy up to 30 days. Our primary outcome was hospitalization rate. The secondary outcomes included ER visit, duration of disease, and complications, such as hypoglycemia, low blood pressure or altered mental status. Results: Of the 206 patients referred to clinics, 103 received standard therapy and 103 treated with combination therapy. There were no significant differences in baseline characteristics, except for slightly higher clinical score in control group (6.92 ± 4.01 control, 4.87 ± 2.92 combination; P <0.0001). Treatment with combination therapy was associated with lower admission rate (5.8% combination, 22.3% control; P = 0.0011), ER visits (7.8% combination, 23.3% control; P = 0.0021) and average duration of symptoms (6.67 ± 2.30 days combination, 18.71 ± 6.49 days control; P =<0.0001). Conclusion: In this prospective cohort study of acutely ill outpatients with COVID-19, the combination of sitagliptin and spironolactone reduced duration of COVID infection and hospital visits better than standard therapeutic approaches. The effects of combination of sitagliptin and spironolactone in COVID-19 patients should be further verified in a double blind, randomized, placebocontrolled trial.
Additional Information Correspondence: Kamyar Asadipooya, MD, Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, KY 40504, USA. Email: kas224@uky.edu Disclosure Summary: The authors have no conflicts of interest to report. Authors' contributions: KA proposed the idea and designed the study. KA, RA, YM and RK wrote the manuscript. MAD, YM, HF, FSRR, AP, and MH collected the data. RA provided statistical analysis and wrote statistical part. All authors approved the final version of the manuscript. .
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J ' 'Clin Endocrinol Metab 103(4):1233–1257', 'journal-title': 'J Clin Endocrinol Metab'}], 'container-title': 'Journal of Endocrinological Investigation', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40618-023-02141-0.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s40618-023-02141-0/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40618-023-02141-0.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 1, 9]], 'date-time': '2024-01-09T19:14:07Z', 'timestamp': 1704827647000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s40618-023-02141-0'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 6, 24]]}, 'references-count': 57, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 1]]}}, 'alternative-id': ['2141'], 'URL': 'http://dx.doi.org/10.1007/s40618-023-02141-0', 'relation': { 'has-preprint': [ { 'id-type': 'doi', 'id': '10.1101/2022.01.21.22269322', 'asserted-by': 'object'}]}, 'ISSN': ['1720-8386'], 'subject': [], 'container-title-short': 'J Endocrinol Invest', 'published': {'date-parts': [[2023, 6, 24]]}, 'assertion': [ { 'value': '6 February 2023', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '16 June 2023', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '24 June 2023', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'The authors have declared that no conflict of interest exists.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflict of interest'}}, { 'value': 'IRCT registration number: IRCT20201003048904N2, Registration date: December 10, ' '2020.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Iranian registry of clinical trial'}}]}
Late treatment
is less effective
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