Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis
Bramante et al.
, Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis
, The Lancet Healthy Longevity, doi:10.1016/S2666-7568(20)30033-7
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, 7.2% lower, RR 0.93, p = 0.15, treatment 394 of 2,333 (16.9%), control 791 of 3,923 (20.2%), NNT 31, odds ratio converted to relative risk, PSM, all patients.
risk of death, 24.1% lower, OR 0.76, p = 0.02, treatment 1,129, control 2,173, PSM, women, RR approximated with OR.
risk of death, 3.5% higher, OR 1.03, p = 0.75, treatment 1,204, control 1,750, PSM, men, RR approximated with OR.
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.
Metformin and risk of mortality in patients hospitalised
with COVID-19: a retrospective cohort analysis
Carolyn T Bramante*, Nicholas E Ingraham*, Thomas A Murray, Schelomo Marmor, Shane Hovertsen, Jessica Gronski, Chace McNeil,
Ruoying Feng, Gabriel Guzman, Nermine Abdelwahab, Samantha King, Leonardo Tamariz, Thomas Meehan, Kathryn M Pendleton,
Bradley Benson, Deneen Vojta*, Christopher J Tignanelli*
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.
Funding National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Patient-Centered
Outcomes Research Institute; Minnesota Learning Health System Mentored Training Program, M Health Fairview
Institutional Funds; National Center for Advancing Translational Sciences; and National Cancer Institute.
Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, 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
provide treatment protocols.