Metformin at the time of Covid-19 infection and risk of Long Covid: A Target Trial Emulation Study
BACKGROUND
Our objective was to evaluate metformin prescribed at the time of SARS-CoV-2 infection on the risk of developing Long Covid (LC) in electronic health record data.
METHODS
We conducted a new user analysis of metformin prescribed within 6 days of documented infection with severe acute respiratory coronavirus syndrome 2 (SARS-CoV- 2) versus experimental control: prescription for fluvoxamine, fluticasone, ivermectin, or montelukast.
INCLUSION CRITERIA
a clinic visit in the 0- 6 months and the 6-12 months before infection. Exclusion criteria: metformin or control within 12 months. Primary outcome: LC or death (LC/D), to address death as a competing risk, among patients prescribed drug within Days 0-6 of infection. LC was defined by diagnosis code or computable phenotype. We used entropy balancing to estimate the average treatment effect with a weighted log linear model.
RESULTS
After weighting, there were 248 in the metformin and control groups; the average age was 53 (16); 16% were Black; and 16% were Hispanic. In the primary analysis, 10/248 (4.0%) in the metformin group developed LC/D vs. 21/248 (8.5%) in the control group, adjusted risk ratio (aRR) 0.47 (95% CI 0.25 to 0.89). For prescriptions on Days 0-1 relative to infection, aRR was 0.39 (95% CI 0.12-1.24); for prescriptions on Days 0-14 the aRR was 0.75 (95% CI 0.52-1.08).
CONCLUSIONS
In this observational analysis, metformin prescribed within a week of documented SARS-CoV-2 infection was associated with a 53% lower risk of LC over 6 months than comparator medications. Any risk reduction between 75% to 11% is highly compatible with our data. This analysis of electronic health record diagnoses is important for the reproducibility of clinical trial results that ascertained the same outcome but via participant-report.
Web | DOI | PDF | Preprint: Authorea | Open Access
Carolyn Bramante; John B Buse; Jared D Huling; Christopher Lindsell; Thomas Stewart; Russell L Rothman; David Sahner; Sarah E Dunsmore; Eric Topol; Talia D Wiggen; Steve Makkar; Andrew Toler; Taylor Estepp; Steven Johnson
BACKGROUND
Our objective was to evaluate metformin prescribed at the time of SARS-CoV-2 infection on the risk of developing Long Covid (LC) in electronic health record data.
METHODS
We conducted a new user analysis of metformin prescribed within 6 days of documented infection with severe acute respiratory coronavirus syndrome 2 (SARS-CoV- 2) versus experimental control: prescription for fluvoxamine, fluticasone, ivermectin, or montelukast.
INCLUSION CRITERIA
a clinic visit in the 0- 6 months and the 6-12 months before infection. Exclusion criteria: metformin or control within 12 months. Primary outcome: LC or death (LC/D), to address death as a competing risk, among patients prescribed drug within Days 0-6 of infection. LC was defined by diagnosis code or computable phenotype. We used entropy balancing to estimate the average treatment effect with a weighted log linear model.
RESULTS
After weighting, there were 248 in the metformin and control groups; the average age was 53 (16); 16% were Black; and 16% were Hispanic. In the primary analysis, 10/248 (4.0%) in the metformin group developed LC/D vs. 21/248 (8.5%) in the control group, adjusted risk ratio (aRR) 0.47 (95% CI 0.25 to 0.89). For prescriptions on Days 0-1 relative to infection, aRR was 0.39 (95% CI 0.12-1.24); for prescriptions on Days 0-14 the aRR was 0.75 (95% CI 0.52-1.08).
CONCLUSIONS
In this observational analysis, metformin prescribed within a week of documented SARS-CoV-2 infection was associated with a 53% lower risk of LC over 6 months than comparator medications. Any risk reduction between 75% to 11% is highly compatible with our data. This analysis of electronic health record diagnoses is important for the reproducibility of clinical trial results that ascertained the same outcome but via participant-report.
Web | DOI | PDF | Preprint: Authorea | Open Access