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Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19 - 02/11/21

Doi : 10.1016/j.diabet.2020.101216 
Jean-Daniel Lalau a, b, , Abdallah Al-Salameh a, b, , Samy Hadjadj c, Thomas Goronflot d, Nicolas Wiernsperger e, Matthieu Pichelin c, Ingrid Allix f, Coralie Amadou g, Olivier Bourron h, Thierry Duriez i, Jean-François Gautier j, Anne Dutour k, Céline Gonfroy l, Didier Gouet m, Michael Joubert n, Ingrid Julier o, Etienne Larger p, Lucien Marchand q, Michel Marre r, Laurent Meyer s, Frédérique Olivier t, Gaëtan Prevost u, Pascale Quiniou v, Christelle Raffaitin-Cardin w, Ronan Roussel x, Pierre-Jean Saulnier y, Dominique Seret-Begue z, Charles Thivolet aa, Camille Vatier bb, Rachel Desailloud a, b, Matthieu Wargny d, Pierre Gourdy cc, 1, Bertrand Cariou c, 1

for the CORONADO investigators2

  For full list see Appendix; see supplementary materials associated with this article on line.

a Department of Endocrinology, Diabetes Mellitus and Nutrition, Amiens University Hospital, 80054 Amiens, France 
b PériTox = UMR_I 01, University of Picardie Jules Verne, Amiens, France 
c Département d’Endocrinologie, Diabétologie et Nutrition, l'institut du Thorax, Inserm, CNRS, UNIV Nantes, CHU Nantes, Hôpital Guillaume et René Laennec, 44093 Nantes Cedex 01, France 
d Data Clinic, INSERM, CIC 1413, PHU 11, Nantes University Hospital, Nantes, France 
e Association REMEDES, Ville-sur-Jarnioux, France 
f Département d’Endocrinologie, Diabétologie, Nutrition, CHU Angers, Angers, France 
g Département de Diabétologie, Centre Hospitalier Sud Francilien, Corbeil Essonne, France 
h Sorbonne Université, Assistance Publique Hôpitaux de Paris, Département de Diabétologie, CHU La Pitié Salpêtrière-Charles Foix, Inserm, UMR_S 1138, Centre de Recherche des Cordeliers, Paris 06, Institute of Cardiometabolism and Nutrition ICAN, Paris, France 
i Service D’Endocrinologie, Diabétologie, CH Cholet, Cholet, France 
j Département Diabète et Endocrinologie, Hôpital Lariboisière, Assistance Publique Hôpitaux de Paris, Paris, France 
k Département d’Endocrinologie et de Diabétologie, Hôpital Nord, Assistance Publique Hôpitaux de Marseille, Marseille, France 
l Service d’Endocrinologie, Diabétologie, CH de Pontoise, Pontoise, France 
m Service de Diabétologie, Endocrinologie, Centre Hospitalier de la Rochelle, La Rochelle, France 
n Service Diabétologie-endocrinologie, CHU Caen, Caen, France 
o CH de Ales, Ales, France 
p Université de Paris and AP-HP, Centre Hospitalier Universitaire de Paris, Cochin Hospital, Paris, France 
q Département d’Endocrinologie et de Diabétologie, Centre Hospitalier St. Joseph - St. Luc, Lyon, France 
r Clinique Ambroise Paré Neuilly-sur-Seine, Centre de Recherches des Cordelier, Université Paris Diderot, Paris, France 
s Service d’Endocrinologie, Diabète et Nutrition, HUS - Hôpital Civil, Strasbourg, France 
t Service de Diabétologie, Centre Hospitalier de Cahors, Cahors, France 
u Département d’Endocrinologie, Diabétologie et Maladies Métaboliques, CHU de Rouen, Université de Rouen, Rouen, France 
v CHU de Brest, Brest, France 
w CH Robet Boulin de Libourne, Libourne, France 
x Département d’Endocrinologie, Diabétologie et Nutrition, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Centre de Recherche des Cordeliers, Inserm, U-1138, Université de Paris, Paris, France 
y Centre d’Investigation Clinique CIC 1402, Université de Poitiers, Inserm, CHU de Poitiers, Poitiers, France 
z Service de Diabétologie, CH Gonesse, Gonesse, France 
aa Centre du Diabète DIAB-eCARE, Hospices Civils de Lyon et Laboratoire CarMeN, Inserm, INRA, INSA, Université Claude Bernard Lyon 1, Lyon, France 
bb Assistance Publique Hôpitaux de Paris, Saint-Antoine Hospital, Reference Center of Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Department of Endocrinology, Paris, France 
cc Département d’Endocrinologie, Diabétologie et Nutrition, CHU Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, UMR1048 Inserm/UPS, Université de Toulouse, Toulouse, France 

Corresponding author.

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Abstract

Aims

Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19.

Methods

CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach.

Results

Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P =  0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P <  0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649−1.082] and 0.688 [0.470−1.007] on day 7, then 0.783 [0.615−0.996] and 0.710 [0.537−0.938] on day 28, respectively.

Conclusion

Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.

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Keywords : COVID-19, Death, Mechanical ventilation, Metformin, Propensity score, Type 2 diabetes


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Vol 47 - N° 5

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