Metformin, Ivermectin, and Fluvoxamine Do Not Prevent Severe COVID-19 Outcomes in Overweight Patients

Treatment with metformin, ivermectin, or fluvoxamine for COVID-19 among non-hospitalized adults did not lead to any observed benefits compared with placebo, according to study findings published in The New England Journal of Medicine (August 2022).

As protection from vaccination against SARS-CoV-2 wanes among the general population, effective outpatient therapies to decrease risk for severe disease are needed.

This phase 3, double-blind, randomized, placebo-controlled trial was conducted at 6 centers in the United States between December 2020 and January 2022. Adults (N=1431) who were classified as overweight or obese with onset of COVID-19 symptoms within 7 days were randomized to receive the following:
  • Metformin plus fluvoxamine
  • Metformin plus ivermectin
  • Metformin plus placebo
  • Placebo plus fluvoxamine
  • Placebo plus ivermectin
  • Placebo plus placebo
The dosing for metformin was increased over 6 days to 15 mg for 14 days, ivermectin was given as 390-470 μg/kg for 3 days, and fluvoxamine as 50 mg twice a day for 14 days. The primary endpoint was the composite rates of severe COVID-19, defined as ≤93% oxygen saturation on home oximetry, emergency department (ED) visit, hospitalization, and death.

The study cohorts included patients aged median 43-46 years, 50.9%-57.9% were women, 80.9%-82.9% were White, 46.4%-50.0% had a body mass index (BMI) of 30 kg/m2 or higher, and 65.3%-84.1% were infected with the Delta variant.

Among patients with complete data (n=1305), the primary composite outcome of severe disease, mortality, ED visit, or hospitalization occurred among 25.5%. More of the patients who did not reach the primary endpoint were vaccinated (32.4%) compared with those who met the composite endpoint (19.5%).

Metformin (adjusted odds ratio [aOR], 0.84; 95% CI, 0.66-1.09; P =.19), ivermectin (aOR, 1.05; 95% CI, 0.76-1.45; P =.78), and fluvoxamine (aOR, 0.94; 95% CI, 0.66-1.36; P =.75) were not associated with decreased risk for the primary outcome compared with placebo. Similarly, no study interventions associated with a significant effect for reducing risk for hypoxemia, ED visits, hospitalization, or death compared with placebo.

In addition, patients were asked to record the symptoms they were experiencing every day for 14 days. No evidence supported a faster recovery from symptoms compared with placebo for any intervention. 

This study may have been limited by only recruiting patients aged 30-85 years who were identified as overweight or obese, and these findings may not be generalizable. 

These data do not support the use of metformin, ivermectin, or fluvoxamine as an outpatient intervention to decrease risk for severe COVID-19 disease among adults who were classified as overweight or obese.

The researchers concluded that “None of the trial drugs resulted in a lower severity of symptoms than identically matched placebo.”

Other At-Home Treatments

Many existing drugs like the ones in have been used to treat COVID and often initial reports show success. However, there's concern that these studies took place before the rise of the Omicron variant of COVID-19, which has rendered certain prior treatments ineffective, such as GlaxoSmithKline’s sotrovimab. That newfound ineffectiveness led to the FDA revoking its emergency use authorization for the drug.

You can find a listing of doctors who can prescribe necessary home isolation medications on Find a Provider post. 

There are many COVID-19 treatment protocols out there on the internet. We have reviewed many protocols and believe the FLCCC I-CARE protocol is one of the practical and effective protocols to follow. 

Most of the component treatments in the I-CARE protocol have various mode of actions and may not be affected by the changes in the Omicron variant spike protein.

Always consult your trusted medical professional before you take any medication or supplement.


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