BACKGROUND AND PURPOSE:

• Bramante et al. (The Lancet Infectious Diseases, 2023) examined whether treatment with metformin, ivermectin, or fluvoxamine reduced the risk of long COVID

METHODS:

• Randomized, phase 3 trial
  • 6 sites in the US
  • Trial’s original primary outcome was severe COVID-19 by day 14 (data published separately)
• Participants
  • 30 to 85 years
  • Overweight or obese
  • COVID-19 symptoms <7 days
  • Positive COVID test within 3 days before enrollment
  • Pregnant women were not excluded
  • Exclusions: Low risk of severe COVID-19 (Normal BMI and <30 years)
• Interventions
  • Metformin plus ivermectin
  • Metformin plus fluvoxamine
  • Metformin plus placebo
  • Ivermectin plus placebo
  • Fluvoxamine plus placebo
  • Placebo plus placebo
• Study design
  • Participants were randomly assigned to an intervention group (1:1:1:1:1:1)
  • Trial was blinded
• Primary outcome
  • Long COVID diagnosed by a medical provider

RESULTS:

• 1126 participants were assigned, received a dose of study treatments, and consented to long-term follow-up at day 180
  • Metformin: 564 | Placebo: 562
  • Female: 56.1% (Pregnant: 7.0%)
  • Median age: 45 (IQR, 37 to 54) years
  • Median BMI: 29.8 (IQR, 27.0 to 34.2) kg/m2
• Long COVID diagnoses by day 300: 8.3%
• The incidence of long COVID was reduced in the metformin group vs placebo
  • Metformin: cumulative incidence 6.3% (95% CI, 4.2 to 8.2)
  • Placebo: Cumulative incidence 10.4% (95% CI, 7.8 to 12.9)
  • HR 0.59 (95% CI, 0.39 to 0.89) | P=0.012
• The beneficial effect of metformin was consistent across prespecified subgroups
• When metformin was started within 3 days of symptom onset, the HR of long COVID was even lower
  • Hazard Ratio (HR) 0.37 (95% CI, 0.15 to 0.95)
• Compared to placebo, there was no effect on cumulative incidence of long COVID with
  • Ivermectin: HR 0.99 (95% CI, 0.59 to 1.64)
  • Fluvoxamine: HR 1.36 (95% CI, 0.78 to 2.34)

CONCLUSION:

• In this population of adults with overweight or obesity, metformin reduced the incidence of long COVID compared to placebo (note: pregnant women were not excluded)
• The authors state

In conclusion, early outpatient COVID-19 treatment with metformin decreased the subsequent risk of long COVID by 41.3% during 10-month follow-up

This finding is consistent with the 42.3% reduction in health-care utilisation for severe COVID-19 with metformin in the first 14 days of the trial 

Learn More – Primary Sources:

Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial