COVID-OUT (metformin)
Trial question
What is the role of metformin in patients with COVID-19 infection?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
56.0% female
44.0% male
N = 1323
1323 patients (741 female, 582 male).
Inclusion criteria: nonhospitalized adult patients aged 30-85 years with a confirmed diagnosis of COVID-19 within the past 3 days.
Key exclusion criteria: hospitalization for COVID-19 infection or other reasons; symptom onset > 7 days; immunocompromised patient; hepatic impairment; alcohol use disorder; history of severe kidney disease.
Interventions
N=663 metformin (immediate-release metformin alone, with an increase in dose over 6 days to 1,500 mg/day for 14 days, or metformin in combination with either fluvoxamine or ivermectin).
N=660 placebo (receipt of placebo, fluvoxamine alone or ivermectin alone).
Primary outcome
Composite outcome of hypoxemia, emergency department visit, hospitalization, or death
23.6%
27.4%
27.4 %
20.5 %
13.7 %
6.8 %
0.0 %
Metformin
Placebo
No significant
difference ↔
No significant difference in composite outcome of hypoxemia, emergency department visit, hospitalization, or death (23.6% vs. 27.4%; OR 0.84, 95% CI 0.66 to 1.09).
Secondary outcomes
Significant decrease in composite outcome of emergency department visit, hospitalization, or death (4.1% vs. 7.3%; OR 0.58, 95% CI 0.35 to 0.94).
No significant difference in hospitalization or death from any cause (1.2% vs. 2.7%; OR 0.47, 95% CI 0.2 to 1.11).
No significant difference in hypoxemia (22.6% vs. 24.3%; OR 0.94, 95% CI 0.72 to 1.22).
Conclusion
In nonhospitalized adult patients aged 30-85 years with a confirmed diagnosis of COVID-19 within the past 3 days, metformin was not superior to placebo with respect to the composite outcome of hypoxemia, emergency department visit, hospitalization, or death.
Reference
Carolyn T Bramante, Jared D Huling, Christopher J Tignanelli et al. Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19. N Engl J Med. 2022 Aug 18;387(7):599-610.
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