The "miracle medicine" metformin may add new uses.
On March 6, 2023, a joint study from the University of Minnesota, Johns Hopkins University and other institutions was published on SSRN, a preprint platform owned by The Lancet.
This multicenter, quadruple-blind, parallel-randomized phase III clinical trial confirmed that taking metformin in the early stages of new crown infection can reduce the risk of new crown sequelae by 42%; If metformin is started within 4 days of the onset of symptoms, it further reduces the risk of coronavirus sequelae by 63%.
Screenshot of the paper
How many people will have the sequelae of the new crown?
According to the WHO post-COVID clinical case definition, COVID sequelae are defined as those who develop symptoms 3 months after SARS-CoV-2 infection, last for a minimum of 2 months, and cannot be explained by other diagnoses.
Nature has published an article pointing out that there are up to more than 200 complex symptoms that still plague patients after the new crown is cured. According to a study by the Harvard School of Public Health, more than 40,000 patients included in the study involved more than 50 major symptoms such as extreme exhaustion (58%), headache (44%), attention disorder (27%), hair loss (25%), and respiratory disorders (24%) [1].
Before the Omicron epidemic, data from a large Dutch study released by The Lancet showed that one in every 8 adults infected with new coronavirus pneumonia would have new crown sequelae[2].
In October 2022, a study led by the World Health Organization and co-operated by medical scientists around the world completed the largest study of new crown sequelae to date, analyzing the self-reported follow-up of 1.2 million patients diagnosed with new crown in 22 countries combined with global new crown infection data.
The results showed that 6.2% of the 3 self-reported sequelae symptom groups still had at least 1 sequelae 3 months after symptomatic new crown infection. Of these, 3.7% reported persistent breathing problems, 3.2% with persistent fatigue with physical pain or mood abnormalities, and 2.2% with cognitive abnormalities.
At the same time, the study also showed that 27.5% of hospitalized patients with new crown had sequelae after 3 months of infection, compared with 5.7% of non-hospitalized patients, while ICU monitoring patients had more serious sequelae, reaching 43.1% at 3 months.
Comparison of data from different types of patients Source: Literature 1
How to treat the sequelae of the new crown?
Statistics have shown [3], as of July 28, 2021, a total of 59 studies on the sequelae of the new crown from 22 countries worldwide have been registered with clinical trial management institutions, covering respiratory symptoms, fatigue, cognitive impairment, headache, olfactory disorders and other fields of the new crown sequelae, and the treatment methods studied also include drug therapy, biological agents, dietary supplements, and exercise/psychotherapy.
Unfortunately, so far, most of these studies have been lost, and only a few of the results have been published in peer-reviewed journals, but there are still limitations such as the small number of participants and the unblinded design of the studies.
Latest Research: Does Metformin Really Work?
On March 6, 2023, a team led by Carolyn Bramante, assistant professor at the University of Minnesota School of Medicine, published the long-term follow-up results of a randomized, multicenter, four-blind, parallel-controlled phase III study of COVID-OUT on the Lancet's preprint platform SSRN.
The COVID-OUT study recruited a group of subjects aged 30~85 years old, whose BMI is in the overweight or obese range, who have symptoms of new coronavirus infection in the past 7 days and have tested positive for the new coronavirus at least once in the past 3 days, and were divided into 6 groups and 3 cohorts according to the ratio of 1:1:1:1:1:1, and short-term oral metformin (a hypoglycemic drug) during the new crown virus infection was tested in a placebo-controlled format, The effect of fluvoxamine (an antidepressant) or ivermectin (an antiparasitic drug with anti-inflammatory activity) on the incidence of COVID sequelae up to 10 months after infection.
It is worth noting that the characteristics of the subjects participating in the trial also represent to some extent the people who most often experience the sequelae of the new crown.
Of these, a total of 1323 participants in the metformin group, which the researchers focused on, were eventually included in the study.
After a 10-month follow-up, the researchers included 1125 metformin cohort subjects who had completed at least 6 months of follow-up with the questionnaire into the final analysis.
After excluding confounding factors such as new crown vaccination and the combined use of other drugs, the study found that early oral metformin reduced the risk of sequelae within 300 days of infection in people infected with the new crown virus by 42% compared with placebo (6.3% in the metformin group vs. 10.6% in the placebo group).
In contrast, taking fluvoxamine (10.1% vs. 7.5% in the placebo group) or ivermectin (8% vs. 7.5% in the placebo group) had no significant effect on the incidence of coronavirus sequelae.
At the 60/120/180/240/300th day follow-up, the proportion of patients diagnosed with new crown sequelae in the metformin group and placebo group (Source: Reference 10)
Of note, although participants in the study protocol received metformin treatment for only 6 days, the protective effects of metformin increased over time over a 10-month follow-up period. This means that in the treatment of new coronavirus infection, metformin can make more patients adhere to the drug because of the shorter course of treatment.
The cumulative proportion of patients diagnosed with new crown sequelae in metformin group (blue) and placebo (orange) (Source: Reference 10)
The study, which is currently published in preprint, is still under peer review and, if officially published, would be one of the most impactful results in the treatment of coronavirus sequelae to date.
Eric J. Topol, a professor at The Scripps Research Institute and editor-in-chief of the famous medical media Medscape, said in his blog[11] that the results of the study were "exciting".
Eric believes that although there are currently no other data to replicate this result, the current data from this study is "sufficient to recommend metformin in clinical practice."
"My opinion is yes, as the risk of side effects from taking metformin for 2 weeks is almost zero (both in the trial itself and with decades of experience with metformin for a long time) and at a very low cost." Eric says, "I don't use the word 'breakthrough' lightly. But seeing such significant benefits in current metformin randomized trials, and considering its safety and low cost, I think it's groundbreaking. In other words, unless there is data to the contrary, if I am infected with COVID, I will take metformin at the dose used in this trial for 2 weeks."
However, it is important to further validate the results and determine the population most suitable for metformin therapy before it can be more widely used in clinical practice. For patients with renal insufficiency, taking certain medications, or requiring invasive medical procedures, short-term use of metformin can also cause risks such as lactic acidosis. (Curator: z_popeye | Executive Producer: Gyozua)
Acknowledgements: This article has been professionally reviewed by Zhou Yebin, a doctor of genetics and drug discovery scientist
Source: Visual China
Author: Fang Jingyu
Resources:
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