A new article, which has created a stir in “Covid sciences” circles, was noticed and reported on 3/7/23, when it was still at the “preprint” stage: many news feeds carried it. I have eliminated Scientific terminology and the fine details of the trial protocol, so as to render this very important article easier to understand, by my readers.

The full article was published by CT Bramante et al., on 6/8/23. In case you want to read it, here are the particulars:
“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”, by Carolyn T Bramante, MD, Prof John B Buse, PhD, David M Liebovitz, MD, Jacinda Nicklas, MD, Michael A Puskarich, MD, Ken Cohen MD, Published: June 08, 2023. DOI: https://doi.org/10.1016/S1473-3099(23)00299-2

The authors tested treatment with Metformin, Ivermectin or Fluvoxamine, beginning at 3 days or less following onset of Covid 19 symptoms, to see whether any of those medications would reduce the severity of Covid. Later, the data was applied to the question of reducing the risk of Long Covid, with Metformin.

Trial protocol

A randomized, quadruple blind study was done at 6 sites in the US: overweight or obese adults, age 30 to 85 years, who had active Covid infection, were randomly assigned to receive one of the following combinations:
metformin + placebo,
ivermectin + placebo,
fluvoxamine + placebo
metformin + ivermectin,
metformin + fluvoxamine, or
placebo + placebo.

The trial was begun on 12/30/20, completed on 1/28/22 and registered with ClinicalTrials.gov: the designated trial # is NCT04510194.

Number of participants

Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned to the protocol, as outlined above. People who were already taking one of the study medications or who had already received a COVID-19 treatment were excluded.
1126 patients consented to long-term follow-up and completed at least one follow-up session, at 6 months.
Of the 1126 long-term participants, 1074 (95%) completed a nine-month follow-up. Of these, 632 were female (44 were pregnant and therefore, were not assigned to the fluvoxamine or ivermectin groups). 494 were male.
All were assessed for Long Covid by day 300: Overall, 93 (8·3%) of 1126 participants were diagnosed with long COVID by day 300.

All study drugs were oral medications in tablet form. The metformin dose was titrated over 6 days: 500 mg on day 1, 500 mg twice daily on days 2–5, then 500 mg in the morning and 1000 mg in the evening up to day 14. The ivermectin dose was 390–470 μg/kg per day for 3 days (median 430 μg/kg per day). The fluvoxamine dose was 50 mg on day 1 followed by 50 mg twice daily up to day 14.

The active follow-up period for the trial was 28 days. Beginning at 60 days after randomisation, surveys were sent every 30 days up to day 300 (10 months) after randomisation, via automated email, text message, letter, or call, per patient preference. 10-month follow-up for long COVID was not in the original protocol because long COVID was not a known entity in late 2020. The prespecified secondary endpoint on long COVID was added to the protocol on April 23, 2021,


When metformin was started within 3 days of symptom onset, the HR was 0·37 (95% CI 0·15–0·95). No effect on the incidence of long COVID was produced by Ivermectin or Fluvoxamine, compared with placebo.

The incidence of long COVID by day 300 was 6·3% in participants who received metformin and 10·4% (7·8–12·9) in those who received identical metformin placebo. The metformin beneficial effect was consistent. There was no effect on incidence of long COVID with ivermectin or fluvoxamine, compared with placebo.

Incidence of post-COVID-19 condition (long COVID) diagnoses, 10 months after randomisation

Metformin reduces the incidence of Long Covid by 41%

Graph: Metformin reduces the incidence of Long Covid


Treatment with Metformin, beginning less than 4 days following onset of symptoms, reduced long COVID incidence by about 41%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe.

I am a Toronto-trained Urologist. I practiced in downtown Toronto, from 1977 to 1997, when I went to Saudi Arabia as chief of Urology at the Armed Forces (teaching) hospital in Tabuk. Returning to Toronto in Y2000, I switched to family practice. In 2007, began to prescribe Hormone Restoration Therapy and in 2012, I became a member of the American Academy of Antiaging Medicine [A4M]. I successfully wrote the A4M's written examination in December, 2013 and In May, 2016 I passed the oral examination, for accreditation as a BHRT consultant. In 2014 I began BHRT practice in Collingwood, Ontario and in January, 2017, joined the Stone Tree Naturopathic Clinic. Now I am 82 and have retired, but it seems wasteful to jettison my learning and experience: the medical establishment knows nothing of BHRT / Functonal medicine and I feel obliged to offer my knowledge in the interest of those who are willing to think outside the box. MY QUALIFICATIONS: MB, BS, (from UWI), 1964. LMCC 1969. FRCSC (Urology), 1974. ECFMG 1984. Florida license 1998 [inactive], ABAARM Certification [A4M], 2016. I am a Member of CSAMM [the Canadian Society for Aging and Metabolic Medicine], the OMA&CMA, SUSO, CUA, RCP&S/C. PRACTICE TO DATE: Consultation in Functional Medicine, including assessment of Chronic Fatigue Syndrome, Fibromyalgia, Andropause, Menopause, Teenage and Postpartum Depression/Panic Attacks, Thyroid Hormone malfunction, Infertility, Sexual Dysfunction and “the Undiagnosable”. ALL ARE WELCOME to read, comment or question!

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