Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19

Lalau, Jean–Daniel; Al‐Salameh, Abdallah; Hadjadj, Samy; Goronflot, Thomas; Wiernsperger, Nicolas; Pichelin, Matthieu; Allix, Ingrid; Amadou, Coralie; Bourron, Olivier; Duriez, Thierry; Gautier, Jean‐François; Dutour, Anne; Gonfroy, Céline; Gouet, D.; Joubert, Michaël; Julier, Ingrid; Larger, Étienne; Marchand, Lucien; Marre, Michel; Meyer, Laurent; Olivier, Frédérique; Prévost, Gaëtan; Quiniou, Pascale; Raffaitin‐Cardin, Christelle; Roussel, Ronan; Saulnier, Patrick; Seret‐Bégué, Dominique; Thivolet, Charles; Vatier, Camille; Desailloud, Rachel; Wargny, Matthieu; Gourdy, Pierre; Cariou, Bertrand

doi:10.1016/j.diabet.2020.101216

Cited by 86 publications

(96 citation statements)

References 40 publications

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“…The question of the safety of the different glucose-lowering therapies in the context of COVID-19 is among the key questions that patients with T2DM and physicians have been asking since the beginning of the pandemic and the identification of the negative effect of diabetes mellitus in COVID-19 prognosis. The present study helps to consolidate previously reported findings, such as the beneficial association between use of metformin and decreased COVID-19-related mortality, from the French nationwide CORONADO study 2 and from a meta-analysis 3 . This study also consolidates the the deleterious association with insulin, which had already been suggested in a Chinese study 4 .…”

supporting

confidence: 84%

“…As indicated by Rory Collins and colleagues 6 , evidence of any effect of a medication derived from observational studies must be considered only if the association at least doubles the outcomes. This requirement was neither consistently evidenced in the present study 1 , even after looking at the low and high estimates of the hazard ratio, nor in most previous epidemiological studies 2 – 4 .…”

contrasting

confidence: 72%

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Glucose-lowering treatments and COVID-19 mortality in T2DM

Hadjadj

Wargny

2021

Nat Rev Endocrinol

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supporting

confidence: 84%

contrasting

confidence: 72%

Glucose-lowering treatments and COVID-19 mortality in T2DM

Hadjadj

Wargny

2021

Nat Rev Endocrinol

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“…Although the small sample size did not allow for statistical significance using Z-test for proportions, the data trend did show that metformin use improved hospitalization outcomes more than (>) the anti-T2DM alpha-glucosidase inhibitors (26.7%), > thiazolidinediones (22.2%), > sulfonylurea (20.1%), > meglitinides (20.0%), > dipeptidyl peptidase-4 inhibitors (20.0%) and > insulin (12.1%). Subsequent studies examining metformin use in diabetic individuals hospitalized for COVID-19 infection showed an association with a lower risk of death [148,149].…”

Section: Discussionmentioning

confidence: 99%

The Fatty Acid Lipid Metabolism Nexus in COVID-19

Tanner

Alfieri

2021

Viruses

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Enteric symptomology seen in early-stage severe acute respiratory syndrome (SARS)-2003 and COVID-19 is evidence of virus replication occurring in the intestine, liver and pancreas. Aberrant lipid metabolism in morbidly obese individuals adversely affects the COVID-19 immune response and increases disease severity. Such observations are in line with the importance of lipid metabolism in COVID-19, and point to the gut as a site for intervention as well as a therapeutic target in treating the disease. Formation of complex lipid membranes and palmitoylation of coronavirus proteins are essential during viral replication and assembly. Inhibition of fatty acid synthase (FASN) and restoration of lipid catabolism by activation of AMP-activated protein kinase (AMPK) impede replication of coronaviruses closely related to SARS-coronavirus-2 (CoV-2). In vitro findings and clinical data reveal that the FASN inhibitor, orlistat, and the AMPK activator, metformin, may inhibit coronavirus replication and reduce systemic inflammation to restore immune homeostasis. Such observations, along with the known mechanisms of action for these types of drugs, suggest that targeting fatty acid lipid metabolism could directly inhibit virus replication while positively impacting the patient’s response to COVID-19.

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“…Three studies analyzed composite endpoint (mortality and severity) [27,28,40] and metformin was not significantly associated with disease severity and mortality (OR = 0.82, 95% CI: 0.44-1.53, P = 0.025).…”

Section: Metformin and Risk Of Mortality And Severe (Composite Endpoint) Sars-cov-2 Infectionmentioning

confidence: 98%

“…Out of 946 potentially relevant articles, and following application of inclusion criteria, 32 studies were retained including a total of 44306 participants. The included studies were conducted in Austria [14], Belgium [15], China [16][17][18][19][20][21][22][23][24], France [25][26][27], Hong Kong [28], Iraq [29], Italy [30,31], Russia [32]which determines the high relevance of risk factor analysis for outcomes in DM patients to substantiate the strategy for this category of patients. AIM: To assess the effect of clinical and demographic parameters (age, gender, body mass index (BMI, South Korea [33,34], Spain [35,36], UK [37][38][39][40][41] and USA [42][43][44][45].…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Metformin therapy and severity and mortality of SARS-CoV-2 infection: a meta-analysis

Oscanoa

Amado

Vidal³

et al. 2021

Clinical Diabetology

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background. It has been postulated that metformin could have anti-SARS-CoV-2 action. this raises the hypothesis that people who take metformin may have lower SARS-CoV-2 severity and/or mortality. Objectives. to conduct a meta-analysis of the association between the use of Metformin and risk of severity and mortality in SARS-CoV-2 infection. Methods. We searched PubMed, EMbASE, Google scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv and Research Square) for studies published between December 2019 and January 2021. Data was extracted on study location, year of publication, design, number of participants, sex, age at baseline, body mass index, and exposure and outcome definition. Effect statistics were pooled using random effects models with 95% confidence intervals (CI). the quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Results. thirty-two observational studies were included, combining to a total sample of 44306 participants. the mean NOS score of included studies was 7.9. Results suggested that metformin use was associated with a reduced risk of SARS-CoV-2 mortality (OR = 0.56, 95% CI: 0.46-0.68, P < 0.001; 22 studies) but not with disease severity (OR = 0.85, 95% CI: 0.71-1.02, P = 0.077; 15 studies). In the subgroup analysis, metformin reduces the risk of mortality (OR = 0.69, 95% CI: 0.55-0.88; P = 0.002) and severity (OR = 0.83, 95% CI: 0.70-0.97, P = 0.023) in patients aged 70 and above. Conclusions. the use of metformin was associated to lower risk of mortality from SARS-CoV-2 infection. this association does not imply causation and further research is required to clarify potential mechanisms.

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Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19

Cited by 86 publications

References 40 publications

Glucose-lowering treatments and COVID-19 mortality in T2DM

Glucose-lowering treatments and COVID-19 mortality in T2DM

The Fatty Acid Lipid Metabolism Nexus in COVID-19

Metformin therapy and severity and mortality of SARS-CoV-2 infection: a meta-analysis

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