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0 0.5 1 1.5 2+ Mortality, adjusted results 27% Improvement Relative Risk Metformin for COVID-19  Han et al.  META ANALYSIS c19early.org Favors metformin Favors control

Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis

Han et al., Archives of Medical Research, doi:10.1016/j.arcmed.2021.08.002, PROSPERO CRD42020221951
Feb 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 31 studies (23 for metformin) showing metformin was associated with significantly lower mortality and poor composite outcomes in diabetic COVID-19 patients. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and GLP-1RA were not associated with increased mortality risk. Subgroup analysis found home use of metformin was more effective than in-hospital use.
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, 27.0% lower, OR 0.73, p = 0.001, adjusted results, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Han et al., 28 Feb 2022, peer-reviewed, 16 authors, trial PROSPERO CRD42020221951. Contact: drsunchenyu@yeah.net.
This PaperMetforminAll
Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis
Tiantian Han, Shaodi Ma, MD, MSc Chenyu Sun, Huimei Zhang, Guangbo Qu, Yue Chen, Ce Cheng, Eric L Chen, Mubashir Ayaz Ahmed, Keun Young Kim, Raveena Manem, Mengshi Chen, Zhichun Guo, Hongru Yang, Yue Yan, Qin Zhou
Archives of Medical Research, doi:10.1016/j.arcmed.2021.08.002
Background and Aims. During the current Coronavirus Disease 2019 (COVID-19) pandemic, patients with diabetes face disproportionately more. This study was performed to clarify anti-inflammatory effects of anti-diabetic agents on COVID-19 in patients with diabetes. Methods and Results. Relevant literature was searched on 15 databases up to November 14, 2020 and was updated on April 13, 2021. The pooled ORs along with 95% CIs were calculated to evaluate combined effects. 31 studies with 66,914 patients were included in qualitative and quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality (pooled OR = 0.62, 95% CI, 0.50-0.76, p = 0.000) and poor composite outcomes (pooled OR = 0.83, 95% CI, 0.71-0.97, p = 0.022) in diabetic patients with COVID-19. Significance of slight lower mortality remained in sulfonylurea/glinides (pooled OR = 0.93, 95% CI, 0.89-0.98, p = 0.004), but of poor composite outcomes was not (pooled OR = 1.48, 95% CI, 0.61-3.60, p = 0.384). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR = 0.95, 95% CI, 0.72-1.26, p = 0.739) or poor composite outcomes (pooled OR = 1.27, 95% CI, 0.91-1.77, p = 0.162) of COVID-19 in diabetic patients. Conclusion. Metformin might be beneficial in decreasing mortality and poor composite outcomes in diabetic patients infected with SARS-CoV-2. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and GLP-1RA would not seem to be adverse. There was insufficient evidence to conclude effects of other anti-diabetic agents. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed.
Supplementary Materials Supplementary material associated with this article can be found, in the online version, at doi: 10.1016/j.arcmed.2021. 08.002.
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'first-page': '2999', 'journal-title': 'Diabetes Care', 'key': '10.1016/j.arcmed.2021.08.002_bib0040', 'volume': '43', 'year': '2020'}, { 'DOI': '10.1093/ehjcvp/pvaa098', 'article-title': 'The association of hypertension and diabetes pharmacotherapy with ' 'COVID-19 severity and immune signatures: an observational study', 'author': 'Dalan', 'doi-asserted-by': 'crossref', 'first-page': 'e48', 'journal-title': 'Eur Heart J Cardiovasc Pharmacother', 'key': '10.1016/j.arcmed.2021.08.002_bib0041', 'volume': '7', 'year': '2021'}, { 'DOI': '10.1111/dom.14329', 'article-title': 'Comparable COVID-19 outcomes with current use of GLP-1 receptor ' 'agonists, DPP-4 inhibitors, or SGLT-2 inhibitors among patients with ' 'diabetes who tested positive for SARS-CoV-2', 'author': 'Israelsen', 'doi-asserted-by': 'crossref', 'first-page': '1397', 'journal-title': 'Diabetes Obes Metab', 'key': '10.1016/j.arcmed.2021.08.002_bib0042', 'volume': '23', 'year': '2021'}, { 'DOI': '10.2337/dc20-1824', 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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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