Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 34927127 · doi:10.1016/j.lana.2021.100142
What was done
A placebo-controlled, randomized adaptive platform trial (TOGETHER Trial) conducted in Brazil evaluated early outpatient treatment with metformin for symptomatic COVID-19 in adults aged over 50 years or with at least one risk factor for disease severity. Participants were randomly assigned to oral metformin (750 mg twice daily for 10 days; n = 215) or matching placebo (twice daily for 10 days; n = 203). The primary outcome was hospitalization at 28 days post-randomization, defined as retention in a COVID-19 emergency setting for >6 hours or transfer to a tertiary hospital. Secondary outcomes included viral clearance at day 7, time to hospitalization, mortality, and adverse drug reactions.
What was found
The trial stopped enrollment early for futility after recruiting 418 participants (median age 52 years, 56.0% >50 years, 57.2% female). Metformin showed no difference compared to placebo in the primary outcome of 28-day hospitalization or emergency retention (relative risk 1.14, 95% Credible Interval 0.73 to 1.81; probability of superiority 0.28). There was also no significant difference in day 7 viral clearance (odds ratio 0.99, 95% CI 0.88 to 1.11) or other secondary outcomes.
Why it matters
Early outpatient treatment with metformin failed to prevent clinical deterioration or hospital admission in symptomatic high-risk COVID-19 patients.
Limits
The trial was terminated early for futility, limiting final sample size (n = 418) and power for secondary outcomes like mortality. The study was conducted in a single country (Brazil), evaluated only one dosing regimen, and is indexed as a retracted publication in PubMed.
Cited by
- supports In the TOGETHER adaptive platform trial evaluating repurposed treatments for COVID-19, study arms for hydroxychloroquine, lopinavir-ritonavir, and metformin were halted due to a lack of clinical efficacy.