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Antidiabetic agent use and clinical outcomes in patients with diabetes hospitalized for COVID-19: a systematic review and meta-analysis

Keels et al., Frontiers in Endocrinology, doi:10.3389/fendo.2024.1482853, PROSPERO CRD42023476297
Jan 2025  
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Mortality 59% Improvement Relative Risk Metformin for COVID-19  Keels et al.  META ANALYSIS c19early.org Favorsmetformin Favorscontrol 0 0.5 1 1.5 2+
Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020, now with p < 0.00000000001 from 102 studies.
No treatment is 100% effective. Protocols combine treatments.
5,200+ studies for 112 treatments. c19early.org
Systematic review and meta-analysis of 35 studies showing lower mortality with metformin and DPP-4 inhibitor treatment for COVID-19 patients with diabetes.
23 meta analyses show significant improvements with metformin for mortality1-22, hospitalization7,13, progression1, and severity8,9,13.
Currently there are 102 metformin for COVID-19 studies, showing 37% lower mortality [33‑41%], 33% lower ventilation [17‑46%], 17% lower ICU admission [6‑26%], 17% lower hospitalization [11‑23%], and 5% fewer cases [-4‑13%].
risk of death, 59.0% lower, RR 0.41, p = 0.002.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Keels et al., 6 Jan 2025, peer-reviewed, 4 authors, trial PROSPERO CRD42023476297. Contact: keelsj@bc.edu, jordan.keels@bc.edu.
This PaperMetforminAll
Antidiabetic agent use and clinical outcomes in patients with diabetes hospitalized for COVID-19: a systematic review and meta-analysis
Jordan N Keels, Isabella R Mcdonald, Christopher S Lee, Andrew A Dwyer
Frontiers in Endocrinology, doi:10.3389/fendo.2024.1482853
Background: The effect of antidiabetic agents on mortality outcomes is unclear for individuals with diabetes mellitus (DM) who are hospitalized for COVID-19. Purpose: To examine the relationship between antidiabetic agent use and clinical outcomes in individuals with DM hospitalized for COVID-19. Methods: A systematic review of the literature (2020-2024) was performed across five databases. Included articles reported primary research (English) reporting clinical outcomes of adult patients (≥18 yrs.) with DM receiving antidiabetic agents who were hospitalized for COVID-19. Following PRISMA guidelines articles underwent independent dual review. Quality appraisal was completed for included studies. Independent reviewers used a structured data extraction form to retrieve relevant data. Aggregated data were synthesized by treatment regimen and reported descriptively. Random effects meta-analyses were performed to assess relative risk and prevalence of mortality. Results: After removing duplicates, title and abstract screening of 4,898 articles identified 118 articles for full-text review and 35 articles were retained for analysis. Included articles were primarily from China (15/35, 43%) and retrospective in nature (31/35, 89%). Fourteen studies (40%) assessed multiple antidiabetic agents, fifteen studies (42%) focused on metformin, three studies (9%) assessed the use of DPP-4 inhibitors, and three single studies (9%) investigated the use of insulin, TZD, and SGLT2 inhibitors. Despite differences among studies, the overall relative risk of mortality among metformin and DPP-4 inhibitor users was 0.432 (95% CI = 0.268-0.695, z = 3.45, p < 0.001) and the overall prevalence of mortality among all antidiabetic users was 16% (95% CI = 13%-19%, z = 10.70, p < 0.001). Conclusions and implications: Synthesis of findings suggest that patients who remained on oral agents (with/without supplemental insulin therapy) exhibited decreased mortality and lower inflammatory markers. Results indicate that
Author contributions Funding The author(s) declare financial support was received for the research, authorship, and/or publication of article. This study was funded by the Endocrine Nurses Society. 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. Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2024. 1482853/full#supplementary-material .
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Included articles ' 'reported primary research (English) reporting clinical outcomes of adult patients (≥18 yrs.) ' 'with DM receiving antidiabetic agents who were hospitalized for COVID-19. Following PRISMA ' 'guidelines articles underwent independent dual review. Quality appraisal was completed for ' 'included studies. Independent reviewers used a structured data extraction form to retrieve ' 'relevant data. Aggregated data were synthesized by treatment regimen and reported ' 'descriptively. Random effects meta-analyses were performed to assess relative risk and ' 'prevalence of ' 'mortality.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>After ' 'removing duplicates, title and abstract screening of 4,898 articles identified 118 articles ' 'for full-text review and 35 articles were retained for analysis. Included articles were ' 'primarily from China (15/35, 43%) and retrospective in nature (31/35, 89%). Fourteen studies ' '(40%) assessed multiple antidiabetic agents, fifteen studies (42%) focused on metformin, ' 'three studies (9%) assessed the use of DPP-4 inhibitors, and three single studies (9%) ' 'investigated the use of insulin, TZD, and SGLT2 inhibitors. Despite differences among ' 'studies, the overall relative risk of mortality among metformin and DPP-4 inhibitor users was ' '0.432 (95% CI = 0.268-0.695, z = 3.45, p &amp;lt; 0.001) and the overall prevalence of ' 'mortality among all antidiabetic users was 16% (95% CI = 13%–19%, z = 10.70, p &amp;lt; ' '0.001).</jats:p></jats:sec><jats:sec><jats:title>Conclusions and ' 'implications</jats:title><jats:p>Synthesis of findings suggest that patients who remained on ' 'oral agents (with/without supplemental insulin therapy) exhibited decreased mortality and ' 'lower inflammatory markers. Results indicate that individuals with DM should continue oral ' 'antidiabetic agents with additional basal insulin as needed to improve glycemic control and ' 'reduce mortality. 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Endocrinol.', 'published': {'date-parts': [[2025, 1, 6]]}}
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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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