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0 0.5 1 1.5 2+ Mortality 46% Improvement Relative Risk Metformin for COVID-19  Nguyen et al.  META ANALYSIS c19early.org Favors metformin Favors control

Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis

Nguyen et al., Metabolism, doi:10.1016/j.metabol.2022.155196, PROSPERO CRD42021293064
Jun 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 61 studies showing lower mortality with preadmission metformin (42 studies), GLP-1RA, and SGLT-2i use in COVID-19 patients with diabetes. DPP-4i and insulin use were associated with increased mortality, while sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitor use were mortality neutral. A dose-response analysis showed 19.7% lower mortality odds for each 250 mg/day increase in metformin dose.
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, 46.0% lower, OR 0.54, p < 0.001, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Nguyen et al., 30 Jun 2022, peer-reviewed, 8 authors, trial PROSPERO CRD42021293064. Contact: melisa26@tmu.edu.tw.
This PaperMetforminAll
Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis
Nam Nhat Nguyen, Dung Si Ho, Hung Song Nguyen, Dang Khanh Ngan Ho, Hung-Yuan Li, Chia-Yuan Lin, Hsiao-Yean Chiu, Yang-Ching Chen
Metabolism, doi:10.1016/j.metabol.2022.155196
Background: Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes. Methods: A systematic search of PubMed, EMBASE, Scopus and Web of Science databases was performed to include studies (except case reports and review articles) published until November 30, 2021. We excluded papers regarding in-hospital use of antidiabetic medications. We used a random-effects meta-analysis to calculate the pooled OR (95% CI) and performed a sensitivity analysis to confirm the robustness of the meta-analyses. Main findings: We included 61 studies (3,061,584 individuals), which were rated as having low risk of bias. The OR (95% CI) indicated some medications protective against COVID-related death, including metformin [0.54 (0.47-0.62), I 2 86%], glucagon-like peptide-1 receptor agonist (GLP-1RA) [0.51 (0.37-0.69), I 2 85%], and sodium-glucose transporter-2 inhibitor (SGLT-2i) [0.60 (0.40-0.88), I 2 91%]. Dipeptidyl peptidase-4 inhibitor , I 2 82%] and insulin [1.70 (1.33-2.19), I 2 97%] users were more likely to die during hospitalization. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitor were mortality neutral [0.92 (95% CI 0.83-1.01, I 2 44%), 0.90 (95% CI 0.71-1.14, I 2 46%), and 0.61 (95% CI 0.26-1.45, I 2 77%), respectively]. The sensitivity analysis indicated that our findings were robust. Conclusions: Metformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitors were mortality neutral. These findings can have a large impact on the clinicians' decisions amid the COVID-19 pandemic.
Decreased Han et al. [5] Preadmission + in-hospital 20 0.62 (0.50-0.76) Decreased Hariyanto et al. [74] Preadmission 5 0.54 (0.32-0.90) Decreased Kan et al. [75] Preadmission + in-hospital 15 0.69 (0.55-0.86) Decreased Kow et al. [76] Preadmission 5 0.62 (0.43-0.89) Decreased Li et al. [77] Preadmission + in-hospital 19 0.66 (0.56-0.78) Decreased Lukito et al. [78] Preadmission 6 0.64 (0.43-0.97) Decreased Oscanoa et al. [79] Preadmission + in-hospital 22 0.56 (0.45-0.68) Decreased Poly et al. [82] Preadmission + in-hospital 16 0.66 (0.54-0. CRediT authorship contribution statement NNN conceived of the original idea, performed meta-analyses, metaregression, sensitivity analyses, interpreted data, and wrote the first manuscript. DSH, HSN, and DKNH performed the systematic search, study selection, risk of bias assessment, and data extraction. HYC and YCC verified the analytical methods, supervised the findings of this work, and contributed to the revisions of the final manuscript. HYL and CYL provided clinical advice on the interpretation of the data and contributed to the revisions of the final manuscript. All authors approved the final manuscript as submitted and have agreed to be accountable for all aspects of the work. YCC is the guarantor of this work. Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose. All authors declare that there are no relationships or activities that might bias, or be..
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'key': '10.1016/j.metabol.2022.155196_bb0270', 'volume': '18', 'year': '2020'}, { 'article-title': 'Obesity, old age, and frailty are the true risk factors for COVID-19 ' 'mortality and not chronic disease or ethnicity', 'author': 'Philipose', 'journal-title': 'medRxiv', 'key': '10.1016/j.metabol.2022.155196_bb0275', 'year': '2020'}, { 'DOI': '10.1093/gerona/glab124', 'article-title': 'Cardiometabolic therapy and mortality in very old patients with ' 'diabetes hospitalized due to COVID-19', 'author': 'Ramos-Rincón', 'doi-asserted-by': 'crossref', 'first-page': 'e102', 'issue': '8', 'journal-title': 'J Gerontol A Biol Sci Med Sci', 'key': '10.1016/j.metabol.2022.155196_bb0280', 'volume': '76', 'year': '2021'}, { 'article-title': 'Retrospective assessment of treatments of hospitalized Covid-19 ' 'patients', 'author': 'Ravindra', 'journal-title': 'medRxiv', 'key': '10.1016/j.metabol.2022.155196_bb0285', 'year': '2021'}, { 'DOI': '10.1080/07435800.2020.1856865', 'article-title': 'Insulin use, diabetes control, and outcomes in patients with COVID-19', 'author': 'Riahi', 'doi-asserted-by': 'crossref', 'first-page': '45', 'issue': '2', 'journal-title': 'Endocr Res', 'key': '10.1016/j.metabol.2022.155196_bb0290', 'volume': '46', 'year': '2021'}, { 'DOI': '10.1016/j.diabres.2021.108753', 'article-title': 'Unexpectedly lower mortality rates in COVID-19 patients with and ' 'without type 2 diabetes in Istanbul', 'author': 'Satman', 'doi-asserted-by': 'crossref', 'journal-title': 'Diabetes Res Clin Pract', 'key': '10.1016/j.metabol.2022.155196_bb0295', 'volume': '174', 'year': '2021'}, { 'article-title': 'Preadmission usage of metformin and mortality in COVID-19 patients ' 'including the post-discharge period', 'author': 'Saygili', 'first-page': '1', 'journal-title': 'Ir J Med Sci', 'key': '10.1016/j.metabol.2022.155196_bb0300', 'year': '2021'}, { 'DOI': '10.14341/probl12458', 'article-title': 'Diabetes and COVID-19: analysis of the clinical outcomes according to ' 'the data of the Russian diabetes registry', 'author': 'Shestakova', 'doi-asserted-by': 'crossref', 'first-page': '35', 'issue': '1', 'journal-title': 'Probl Endokrinol (Mosk)', 'key': '10.1016/j.metabol.2022.155196_bb0305', 'volume': '66', 'year': '2020'}, { 'DOI': '10.1016/j.numecd.2020.09.028', 'article-title': 'Are diabetes and its medications risk factors for the development of ' 'COVID-19? Data from a population-based study in Sicily', 'author': 'Silverii', 'doi-asserted-by': 'crossref', 'first-page': '396', 'issue': '2', 'journal-title': 'Nutr Metab Cardiovasc Dis', 'key': '10.1016/j.metabol.2022.155196_bb0310', 'volume': '31', 'year': '2021'}, { 'DOI': '10.1111/dom.14256', 'article-title': 'COVID-19 fatality prediction in people with diabetes and prediabetes ' 'using a simple score upon hospital admission', 'author': 'Sourij', 'doi-asserted-by': 'crossref', 'first-page': '589', 'issue': '2', 'journal-title': 'Diabetes Obes Metab.', 'key': '10.1016/j.metabol.2022.155196_bb0315', 'volume': '23', 'year': '2021'}, { 'DOI': '10.1016/j.diabres.2020.108444', 'article-title': 'Use of DPP4 inhibitors in Italy does not correlate with diabetes ' 'prevalence among COVID-19 deaths', 'author': 'Strollo', 'doi-asserted-by': 'crossref', 'journal-title': 'Diabetes Res Clin Pract', 'key': '10.1016/j.metabol.2022.155196_bb0320', 'volume': '171', 'year': '2021'}, { 'DOI': '10.1186/s13098-021-00695-8', 'article-title': 'Outcome and death risk of diabetes patients with Covid-19 receiving ' 'pre-hospital and in-hospital metformin therapies', 'author': 'Tamura', 'doi-asserted-by': 'crossref', 'first-page': '76', 'issue': '1', 'journal-title': 'Diabetol Metab Syndr', 'key': '10.1016/j.metabol.2022.155196_bb0325', 'volume': '13', 'year': '2021'}, { 'DOI': '10.2337/dc21-1351', 'article-title': 'Prior glucose-lowering medication use and 30-day outcomes among 64,892 ' 'veterans with diabetesand COVID-19', 'author': 'Wander', 'doi-asserted-by': 'crossref', 'journal-title': 'Diabetes Care', 'key': '10.1016/j.metabol.2022.155196_bb0330', 'year': '2021'}, { 'DOI': '10.1186/s13045-020-00934-x', 'article-title': 'A tertiary center experience of multiple myeloma patients with ' 'COVID-19: lessons learned and the path forward', 'author': 'Wang', 'doi-asserted-by': 'crossref', 'first-page': '94', 'issue': '1', 'journal-title': 'J Hematol Oncol', 'key': '10.1016/j.metabol.2022.155196_bb0335', 'volume': '13', 'year': '2020'}, { 'DOI': '10.1210/clinem/dgab067', 'article-title': 'Association of Metformin with susceptibility to COVID-19 in people with ' 'type 2 diabetes', 'author': 'Wang', 'doi-asserted-by': 'crossref', 'first-page': '1255', 'issue': '5', 'journal-title': 'J Clin Endocrinol Metab', 'key': '10.1016/j.metabol.2022.155196_bb0340', 'volume': '106', 'year': '2021'}, { 'DOI': '10.1007/s00125-020-05351-w', 'article-title': 'Predictors of hospital discharge and mortality in patients with ' 'diabetes and COVID-19: updated results from the nationwide CORONADO ' 'study', 'author': 'Wargny', 'doi-asserted-by': 'crossref', 'first-page': '778', 'issue': '4', 'journal-title': 'Diabetologia', 'key': '10.1016/j.metabol.2022.155196_bb0345', 'volume': '64', 'year': '2021'}, { 'article-title': 'Use of DPP4i reduced odds of clinical deterioration and ' 'hyperinflammatory syndrome in COVID-19 patients with type 2 diabetes: ' 'propensity score 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outcomes of ' 'COVID-19: narrative review and meta-analysis', 'author': 'Bonora', 'doi-asserted-by': 'crossref', 'first-page': '1379', 'issue': '7', 'journal-title': 'J Endocrinol Invest', 'key': '10.1016/j.metabol.2022.155196_bb0365', 'volume': '44', 'year': '2021'}, { 'article-title': 'Metformin use is associated with reduced mortality rate from ' 'coronavirus disease 2019 (COVID-19) infection', 'author': 'Hariyanto', 'journal-title': 'Obes Med', 'key': '10.1016/j.metabol.2022.155196_bb0370', 'volume': '19', 'year': '2020'}, { 'DOI': '10.3389/fendo.2021.708494', 'article-title': 'Mortality risk of antidiabetic agents for type 2 diabetes with ' 'COVID-19: a systematic review and meta-analysis', 'author': 'Kan', 'doi-asserted-by': 'crossref', 'journal-title': 'Front Endocrinol (Lausanne)', 'key': '10.1016/j.metabol.2022.155196_bb0375', 'volume': '12', 'year': '2021'}, { 'DOI': '10.1002/jmv.26498', 'article-title': 'Mortality risk with preadmission metformin use in patients with ' 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'Metformin use is associated with decreased mortality in COVID-19 ' 'patients with diabetes: evidence from retrospective studies and ' 'biological mechanism', 'author': 'Poly', 'doi-asserted-by': 'crossref', 'issue': '16', 'journal-title': 'J Clin Med', 'key': '10.1016/j.metabol.2022.155196_bb0410', 'volume': '10', 'year': '2021'}, { 'DOI': '10.1016/j.dsx.2021.03.027', 'article-title': 'Dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in coronavirus ' 'disease 2019 (COVID-19) - a systematic review, meta-analysis, and ' 'meta-regression', 'author': 'Rakhmat', 'doi-asserted-by': 'crossref', 'first-page': '777', 'issue': '3', 'journal-title': 'Diabetes Metab Syndr', 'key': '10.1016/j.metabol.2022.155196_bb0415', 'volume': '15', 'year': '2021'}, { 'DOI': '10.1016/j.diabet.2020.07.006', 'article-title': 'Metformin and COVID-19: from cellular mechanisms to reduced mortality', 'author': 'Scheen', 'doi-asserted-by': 'crossref', 'first-page': '423', 'issue': '6', 'journal-title': 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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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