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0 0.5 1 1.5 2+ Mortality 26% Improvement Relative Risk Metformin for COVID-19  Chen et al.  META ANALYSIS c19early.org Favors metformin Favors control

The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis

Chen et al., Frontiers in Endocrinology, doi:10.3389/fendo.2022.895458, PROSPERO CRD42021288200
May 2022  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
 
*, now known with p < 0.00000000001 from 89 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19early.org
Meta-analysis of 42 studies (25 for metformin) with 7 antidiabetic agents, showing metformin, DPP4i, SGLT2i, and GLP1RA were associated with lower COVID-19 mortality in patients with diabetes compared to non-users, while insulin was associated with higher mortality.
22 meta analyses show significant improvements with metformin for mortality Chen, Ganesh, Han, Hariyanto, Kan, Kow, Li, Lukito, Ma, Nassar, Nguyen, Oscanoa, Parveen, Petrelli, Poly, Scheen, Schlesinger, Song, Sun, Yang, Zhan, hospitalization Li, Song, progression Yang, and severity Petrelli, Schlesinger, Song.
Currently there are 89 metformin for COVID-19 studies, showing 34% lower mortality [29‑39%], 33% lower ventilation [17‑46%], 16% lower ICU admission [6‑25%], 18% lower hospitalization [11‑24%], and 5% fewer cases [-4‑13%].
risk of death, 26.0% lower, OR 0.74, p < 0.001, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Chen et al., 27 May 2022, peer-reviewed, 5 authors, trial PROSPERO CRD42021288200. Contact: daimengjun@sjtu.edu.cn.
This PaperMetforminAll
The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis
Yidan Chen, Xingfei Lv, Sang Lin, Mohammad Arshad, Mengjun Dai
Frontiers in Endocrinology, doi:10.3389/fendo.2022.895458
Aims: This study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, 2021 and included seven antidiabetic agents. The data were pooled via traditional pairwise meta-analysis and Bayesian network meta-analysis. Results: The pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodiumglucose cotransporter-2 inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists (GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in individuals with diabetes compared to respective nonusers. However, insulin treatment resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease risk (all P>0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had the fifth-highest rank probability of 42.4%, followed by sulfonylurea at 45.1%. Conclusion: Metformin, DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk in individuals with diabetes, while insulin might be related to increased mortality risk. Sulfonylurea and TZDs treatments were not associated with
AUTHOR CONTRIBUTIONS YC, XL, and SL: Conceptualization, methodology, data curation, investigation, and writing -original draft preparation. MA and MD: Supervision, writing -reviewing and editing, and funding acquisition. All authors contributed to the article and approved the submitted version. SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2022.895458/ full#supplementary-material Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's Note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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{ 'DOI': '10.3389/fendo.2022.895458', 'ISSN': ['1664-2392'], 'URL': 'http://dx.doi.org/10.3389/fendo.2022.895458', 'abstract': '<jats:sec><jats:title>Aims</jats:title><jats:p>This study aimed to assess the impact of ' 'different antidiabetic agents on individuals with diabetes and ' 'COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We searched ' 'PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, ' '2021 and included seven antidiabetic agents. The data were pooled ' '<jats:italic>via</jats:italic> traditional pairwise meta-analysis and Bayesian network ' 'meta-analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The ' 'pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), ' 'dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodium-glucose cotransporter-2 ' 'inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists ' '(GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in ' 'individuals with diabetes compared to respective non-users. However, insulin treatment ' 'resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in ' 'sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. ' 'Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, ' 'sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease ' 'risk (all P&amp;gt;0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and ' 'SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). ' 'Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third ' 'and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had ' 'the fifth-highest rank probability of 42.4%, followed by sulfonylurea at ' '45.1%.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Metformin, ' 'DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk ' 'in individuals with diabetes, while insulin might be related to increased mortality risk. ' 'Sulfonylurea and TZDs treatments were not associated with mortality. None of the antidiabetic ' 'agents studied were associated with the risk of severe disease. Additionally, GLP1RA probably ' 'had the most significant protective effect against death, followed by SGLT2i and ' 'metformin.</jats:p></jats:sec><jats:sec><jats:title>Systematic Review ' 'Registration</jats:title><jats:p>PROSPERO (CRD42021288200)</jats:p></jats:sec>', 'alternative-id': ['10.3389/fendo.2022.895458'], 'author': [ {'affiliation': [], 'family': 'Chen', 'given': 'Yidan', 'sequence': 'first'}, {'affiliation': [], 'family': 'Lv', 'given': 'Xingfei', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Lin', 'given': 'Sang', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Arshad', 'given': 'Mohammad', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Dai', 'given': 'Mengjun', 'sequence': 'additional'}], 'container-title': 'Frontiers in Endocrinology', 'container-title-short': 'Front. 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Questions and Dilemmas Regarding Early ' 'Short-Term Insulin Treatment in Type 2 Diabetes Mellitus', 'author': 'Koufakis', 'doi-asserted-by': 'publisher', 'journal-title': 'Expert Opin Biol Ther', 'key': 'B67', 'volume': '18', 'year': '2018'}, { 'DOI': '10.1155/2016/8310516', 'article-title': 'Impact of the Type of Continuous Insulin Administration on Metabolism ' 'in a Diabetic Rat Model', 'author': 'Schaschkow', 'doi-asserted-by': 'publisher', 'journal-title': 'J Diabetes Res', 'key': 'B68', 'volume': '2016', 'year': '2016'}, { 'DOI': '10.1186/1471-2466-14-177', 'article-title': 'Sepsis-Induced Lung Inflammation Is Modulated by Insulin', 'author': 'Filgueiras', 'doi-asserted-by': 'publisher', 'journal-title': 'BMC Pulm Med', 'key': 'B69', 'volume': '14', 'year': '2014'}, { 'DOI': '10.1111/dom.13162', 'article-title': 'A Review of Glp-1 Receptor Agonists: Evolution and Advancement, Through ' 'the Lens of Randomised Controlled Trials', 'author': 'Aroda', 'doi-asserted-by': 'publisher', 'first-page': '22', 'journal-title': 'Diabetes Obes Metab', 'key': 'B70', 'year': '2018'}, { 'DOI': '10.1016/j.rmed.2019.06.015', 'article-title': 'Long-Term Observational Study on the Impact of Glp-1r Agonists on Lung ' 'Function in Diabetic Patients', 'author': 'Rogliani', 'doi-asserted-by': 'publisher', 'first-page': '86', 'journal-title': 'Respir Med', 'key': 'B71', 'volume': '154', 'year': '2019'}, { 'DOI': '10.1007/s11096-021-01256-9', 'article-title': 'Sodium-Glucose Co-Transporter 2 Inhibitors in Covid-19: Meeting at the ' 'Crossroads Between Heart, Diabetes and Infectious Diseases', 'author': 'Koufakis', 'doi-asserted-by': 'publisher', 'journal-title': 'Int J Clin Pharm', 'key': 'B72', 'volume': '43', 'year': '2021'}, { 'DOI': '10.1111/eci.13339', 'article-title': 'Sglt2 Inhibition and Covid-19: The Road Not Taken', 'author': 'Das', 'doi-asserted-by': 'publisher', 'journal-title': 'Eur J Clin Invest', 'key': 'B73', 'volume': '50', 'year': '2020'}], 'reference-count': 73, 'references-count': 73, 'relation': {}, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fendo.2022.895458/full'}}, 'score': 1, 'short-title': [], 'source': 'Crossref', 'subject': [], 'subtitle': [], 'title': 'The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With ' 'Diabetes: A Bayesian Network Meta-Analysis', 'type': 'journal-article', 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'volume': '13'}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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