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0 0.5 1 1.5 2+ Mortality, all 12% Improvement Relative Risk Mortality, women 21% Mortality, men 4% Metformin for COVID-19  Bramante et al.  Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 6,256 patients in the USA No significant difference in mortality Bramante et al., The Lancet Healthy Lo.., Dec 2020 Favors metformin Favors control

Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis

Bramante et al., The Lancet Healthy Longevity, doi:10.1016/S2666-7568(20)30033-7
Dec 2020  
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Retrospective 6,256 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment, statistically significant only for women.
risk of death, 11.6% lower, HR 0.88, p = 0.65, treatment 394 of 2,333 (16.9%), control 791 of 3,923 (20.2%), NNT 31, adjusted per study, multivariable, Cox proportional hazards.
risk of death, 21.5% lower, HR 0.79, p = 0.01, treatment 1,129, control 2,173, adjusted per study, women, multivariable, Cox proportional hazards.
risk of death, 4.3% lower, HR 0.96, p = 0.69, treatment 1,204, control 1,750, adjusted per study, men, multivariable, Cox proportional hazards.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Bramante et al., 3 Dec 2020, retrospective, database analysis, USA, peer-reviewed, 17 authors.
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Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis
Dr Carolyn T Bramante, Nicholas E Ingraham, Thomas A Murray, PhD, S King BS Schelomo Marmor, Shane Hovertsen, Jessica Gronski, MS, D Vojta MD Chace Mcneil, MD Ruoying Feng, MD Gabriel Guzman, MD Nermine Abdelwahab, Samantha King, Leonardo Tamariz, MD Thomas Meehan, Kathryn M Pendleton, Bradley Benson, Deneen Vojta, Christopher J Tignanelli
The Lancet Healthy Longevity, doi:10.1016/s2666-7568(20)30033-7
Background Type 2 diabetes and obesity, as states of chronic inflammation, are risk factors for severe COVID-19. Metformin has cytokine-reducing and sex-specific immunomodulatory effects. Our aim was to identify whether metformin reduced COVID-19-related mortality and whether sex-specific interactions exist. Methods In this retrospective cohort analysis, we assessed de-identified claims data from UnitedHealth Group (UHG)'s Clinical Discovery Claims Database. Patient data were eligible for inclusion if they were aged 18 years or older; had type 2 diabetes or obesity (defined based on claims); at least 6 months of continuous enrolment in 2019; and admission to hospital for COVID-19 confirmed by PCR, manual chart review by UHG, or reported from the hospital to UHG. The primary outcome was in-hospital mortality from COVID-19. The independent variable of interest was home metformin use, defined as more than 90 days of claims during the year before admission to hospital. Covariates were comorbidities, medications, demographics, and state. Heterogeneity of effect was assessed by sex. For the Cox proportional hazards, censoring was done on the basis of claims made after admission to hospital up to June 7, 2020, with a best outcome approach. Propensity-matched mixed-effects logistic regression was done, stratified by metformin use. Findings 6256 of the 15 380 individuals with pharmacy claims data from Jan 1 to June 7, 2020 were eligible for inclusion. 3302 (52•8%) of 6256 were women. Metformin use was not associated with significantly decreased mortality in the overall sample of men and women by either Cox proportional hazards stratified model (hazard ratio [HR] 0•887 [95% CI 0•782-1•008]) or propensity matching (odds ratio [OR] 0•912 [95% CI 0•777-1•071], p=0•15). Metformin was associated with decreased mortality in women by Cox proportional hazards (HR 0•785, 95% CI 0•650-0•951) and propensity matching (OR 0•759, 95% CI 0•601-0•960, p=0•021). There was no significant reduction in mortality among men (HR 0•957, 95% CI 0•82-1•14; p=0•689 by Cox proportional hazards). Interpretation Metformin was significantly associated with reduced mortality in women with obesity or type 2 diabetes who were admitted to hospital for COVID-19. Prospective studies are needed to understand mechanism and causality. If findings are reproducible, metformin could be widely distributed for prevention of COVID-19 mortality, because it is safe and inexpensive.
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