People who vape had worrisome changes in cardiovascular function, even as young adults

Study: Metformin Associated With 41% Decrease In Long Covid, Here Are The Caveats

In a clinical trial, 6·3% of those who had received metformin while infected with the severe acute ... [+] respiratory syndrome coronavirus 2 (SARS-CoV-2) ended up getting diagnosed with long Covid compared to 10.4% of those who had received placebo only. (Photo by Francis Dean/Corbis via Getty Images)

Corbis via Getty Images

Don't go "metformin" any premature conclusions about the results of this study just yet. But a clinical trial described in a June 8 publication in The Lancet Infectious Diseases found that those taking metformin when sick with Covid-19 were 41% less likely to have eventually developed long Covid than those taking only a placebo. In the trial, 6·3% of those who had received metformin ended up getting diagnosed with long Covid compared to 10.4% of those who had received placebo only. That's encouraging news because the long and short of it is that doctors currently don't have any proven treatments for long Covid at their disposal. However, there are a lot of buts, one cannot lie, about the findings from this clinical trial. So, before you "metformin" any plans to take this medication the next time you test positive for Covid-19, first take a closer look at what this study actually found.

Here's a tweet from The Lancet Infectious Diseases on the publication and the trial, which bore the name COVID-OUT:

The goal of the COVID-OUT trial was to see whether taking metformin, fluvoxamine, or ivermectin during the acute phase of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could somehow reduce the risk of later developing long Covid. All three medications have been around for a while to treat other unrelated conditions. Metformin is a medication that's been commonly used to treat diabetes. Fluvoxamine is a commonly-used antidepressant that showed some early promise as a treatment for Covid-19, as I've reported for Forbes back on March 8, 2021, but has yet to be established as an effective Covid-19 treatment. And of horse, you've probably heard of ivermectin. Ivermectin is a medication that's been used for years to treat parasite infections in humans, horses, cows, and other animals. There certainly isn't enough scientific evidence that it can be an effective treatment for Covid-19. That hasn't kept a number of personalities and anonymous social media accounts from continuing to make all sorts of claims about ivermectin until the cows come home.

Long Covid, otherwise known as post-COVID-19 condition, by the way, has been a growing major problem since 2020. It's where you either continue to have symptoms or develop new symptoms weeks, months, and even years after you supposedly recovered from a SARS-CoV-2. It's a major problem because chronically suffering difficulty breathing, chest pain, fevers, headaches, chronic fatigue, "brain fog," anxiety, stress, "pins and needles" sensations, sleep problems, joint pain, diarrhea, tummy pain, or other such symptoms kind of really sucks. It's a major unsolved problem because when it comes to treating long Covid doctors have been sort of throwing their hands in the air, but not in a Timbaland song type of way.

Carolyn Bramante, MD, an Assistant Professor of Medicine at the University of Minnesota Medical School and the first author of The Lancet Infectious Diseases publication called metformin "an inexpensive, safe and widely available drug," in the following tweet from the University of Minnesota Medical School:

Indeed, since metformin has been around for many years and generic versions of it are available, metformin is certainly much less expensive than a completely new medication would be. If you look at the common side effects from metformin, you'll find things like abdominal or stomach discomfort, cough, chills, decreased appetite, and diarrhea. Although no one will say, "Yay, diarrhea," these side effects don't necessarily occur and the medication seems to be in general well-tolerated.

The COVID-OUT trial was a decentralized, randomized, quadruple-blind, parallel-group, phase 3 trial. That may sound like quite a mouthful. But it all makes more sense when you look at each word individually. Decentralized meant that the trial was conducted at six different locations in the United States without one location lording over the others. Randomized meant that study participants were randomly assigned to get one of six treatment combinations as soon as they were enrolled in the trial: metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Quadruple-blind didn't mean that everyone was wearing four blindfolds throughout the trial, which would have made it a bit difficult to conduct the trial. Rather, it meant that none of the four major groups of people involved in the study—study participants, investigators, those providing medical care to the participants, and those assessing the outcomes of the participants—knew which participants were assigned to which treatment group. This helped prevent anyone from consciously or unconsciously showing any bias for or against a particular treatment, which has been a problem for some of the ivermectin studies.

To be enrolled into the trial, all participants had to be experiencing Covid-19 symptoms for fewer than seven days and had had a clearly positive SARS-CoV-2 test within the three days prior. This had to be the first time that they were diagnosed with Covid-19. Of note, all participants had to have body mass indices of over 25 kg/m2, the threshold for being in the overweight category. Recruitment for the trial occurred from December 30, 2020, to January 28, 2022. Each participant then received one of the six treatment combinations as soon as he or she was enrolled in the trial. Then each participant was asked to complete surveys 180, 210, 240, 270, and 300 days after being enrolled in the trial. The surveys asked each participant whether they had received a diagnosis of long Covid from a health care professional.

The researchers were able to initially enroll 1431 people in the trial. However, not all of them made it through the entire trial. Of the 1431 people, 1323 eventually received one of the six combinations of treatments while 1126 ended up completing at least one survey. The ages of these 1126 participants ranged from 30 to 85 years. Around 95% (1074 of the 1126 participants) were followed for at least nine months. A little over half (56·1%) of the participants were female with 44 of them being pregnant. The median age of participants ended up being 45 years while the median body mass index BMI ended up being 29·8 kg/m2.

Many people around the world have continued to suffer Long Covid, which is when symptoms persist at ... [+] least three months beyond the initial SARS-CoV-2 infection. (Photo by Jörg Carstensen/picture alliance via Getty Images)

dpa/picture alliance via Getty Images

Participants started receiving treatments as soon as they were enrolled in the trial, which meant that they were still in the midst of their SARS-CoV-2 infection. Ultimately, 564 of the participants ended up receiving a two-week course of metformin that was titrated up from 500 mg to 1000 mg over the first six days, and 562 ended up receiving a matched placebo.

By Day 300 after their initial SARS-CoV-2 infection, 93 (8·3%) of 1126 participants had been diagnosed with long Covid. However, this incidence was 41% lower (6·3% vs. 10.4%) among those who had received metformin compared to those who had received just placebo (10·4%). The difference was even greater (63% lower) among those who had started taking metformin within three days of first experiencing Covid-19 symptoms.

And surprise, surprise, there was no real difference in long Covid incidence between those who had received ivermectin and those who had received placebo. Fluvoxamine didn't seem to have any overall positive effect as well.

So why might a medication that's typically used to treat diabetes help prevent long Covid? Metformin is useful against diabetes because of the following sweet effects: it can decrease the amount of glucose produced by your liver, decrease the amount glucose absorbed through your intestines, and increase the response of your body tissues to insulin. Those taking metformin also often lose weight as well.

But wait, what does that all have to do with long Covid? Well, several laboratory studies have shown that metformin may work specifically against the SARS-CoV-2. It's been found to inhibit the reproduction of the virus in cell culture and human lung tissue. Keep in mind, though, that you are more than a just bunch of cells or lung tissue. You do have feelings and other things. So just because metformin can keep the virus from reproducing in the lab doesn't meant that it will do the same in live, whole humans.

A protester holds up a placard demanding research into Long Covid-19 during the demonstration. ... [+] (Photo by Martin Pope/SOPA Images/LightRocket via Getty Images)

SOPA Images/LightRocket via Getty Images

Plus, while promising, this clinical trial was exactly one clinical trial. You should never deem something to be an effective treatment based on just one clinical trial. That would have been like calling Los Del Rio the next Beatles right after their song Macarena ascended to number one on the Billboard charts in 1996. People aren't exactly lining up to do the Vámonos que nos vamos at weddings.

Moreover, this clinical trial did not include anyone younger than 30, with a BMI less than 25 kg/m2 or who had had COvid-19 previously. People under 30 do matter, really. So the results from this trial may not be generalizable to the rest of the population.

All in all, there needs to be more real scientific evidence before metformin can be recommended as a Covid-19 treatment. That means more studies and trials are definitely needed. Thank goodness for all the research funding that's been allocated to study Covid-19...Oh wait, that's right, a lot of the money is no longer there.

Full coverage and live updates on the Coronavirus

Side Effects Of Metformin: What You Should Know

Metformin is used to help treat type 2 diabetes. Mild side effects, such as nausea, vomiting, and diarrhea, are common and go away with time. But, some serious side effects may require medical attention.

Metformin is a prescription drug for type 2 diabetes. It belongs to a class of medications called biguanides.

Type 2 diabetes is the result of long-term insulin resistance. This means that your body produces insulin but does not use it efficiently. Insulin resistance can cause blood sugar (glucose) levels to rise to a potentially unsafe level. Over time, high blood sugar can cause complications such as kidney disease, nerve damage, and heart disease.

Metformin doesn't cure diabetes. Instead, it helps lower your blood sugar levels into a safe range.

Doctors may also prescribe metformin off-label to treat polycystic ovary syndrome (PCOS).

Metformin can cause side effects ranging from mild to serious. Most side effects are mild and primarily affect your digestive system. Severe side effects, such as lactic acidosis, are less common but require prompt medical attention.

Here's what you need to know about metformin side effects and when to get medical attention.

Recall of metformin extended release

In 2021, one brand recalled two lots of metformin extended-release tablets from the U.S. Market, as reported by the Food and Drug Administration (FDA).

This is because an unacceptable level of a probable carcinogen (cancer-causing agent) was found in some extended-release metformin tablets.

If you currently take this drug, contact a healthcare professional. They will advise you on whether you should continue to take your medication or whether you need a new prescription.

Metformin causes some common side effects. These can occur when you start taking metformin, but they usually go away over time. Talk with a doctor if these symptoms are severe or cause a problem.

Common side effects of metformin include:

Nausea, vomiting, and diarrhea are common when people start taking metformin, but they usually go away with time.

You can reduce the chances of side effects by taking metformin with a meal. To help reduce your risk of severe diarrhea, a doctor may start you on a low dosage of metformin and increase it slowly.

Doctors may also prescribe metformin to people with PCOS. The drug may help:

Lowering insulin levels can, in turn, improve PCOS symptoms such as irregular cycles and acne. Metformin is used off-label for this purpose. The side effects are the same as for other uses.

Off-label drug use

Off-label drug use means that a drug the FDA has approved for one purpose is being used for a different purpose that the FDA has not yet approved.

A doctor can still use the drug for another purpose because, while the FDA regulates the testing and approval of drugs, it does not regulate the ways doctors use drugs to treat their patients. So, your doctor can prescribe the drug they think is best for your care.

Metformin can potentially cause some serious side effects.

Lactic acidosis

Although it is rare, metformin's most serious side effect is lactic acidosis. Metformin has a boxed warning — also called a black box warning — about this risk. A boxed warning is the most severe warning the FDA issues.

Lactic acidosis is a rare but serious problem resulting from a buildup of metformin in your body, which causes a pH imbalance. It's a medical emergency that must be treated immediately in the hospital.

Symptoms can include:

Contact a doctor right away if you have any symptoms of lactic acidosis. If you have trouble breathing, call 911 or your local emergency number or go to the nearest emergency room.

Metformin-associated lactic acidosis has an estimated death rate of up to 50%.

Taking some other medications, including corticosteroids and blood pressure medications, with metformin may increase your risk of lactic acidosis. See the risk factors section for more information about factors that raise your risk of this complication.

Anemia

Metformin can decrease the levels of vitamin B12 in your body. In rare cases, this can cause anemia (low levels of red blood cells). If you don't get much vitamin B12 or calcium through your diet, you may be at higher risk of having very low vitamin B12 levels.

The more common symptoms of anemia include:

tiredness

dizziness

lightheadedness

If you think you may have anemia, make an appointment with your doctor to have your red blood cell levels checked.

Your vitamin B12 levels may improve if you stop taking metformin or take vitamin B12 supplements. Make sure to talk with the doctor who prescribed metformin before you stop taking it.

Hypoglycemia

Metformin doesn't usually cause low blood sugar (hypoglycemia). However, in rare cases, you may develop hypoglycemia if you combine metformin with:

Call your doctor if you have any symptoms of hypoglycemia, such as:

weakness

tiredness

nausea

vomiting

stomach pain

dizziness

lightheadedness

unusually fast or slow heartbeat

According to the United Kingdom's National Health Service, metformin is usually safe to take while pregnant or nursing, either by itself or with insulin.

Metformin crosses the placenta but has not been linked to increased rates of fetal development issues or complications.

A 2022 study found no long-term negative effects of metformin use during pregnancy. The authors noted that metformin use may result in a fetus being small for its gestational age and recommended caution if there is a risk that a fetus will not get adequate nutrition.

The authors also noted that metformin use in females with PCOS is associated with a reduced risk of negative outcomes.

A 2018 review found no significant difference between the rate of serious adverse events in pregnant females who took either a placebo or metformin. Mild side effects such as nausea, vomiting, and diarrhea were reported more often in those who took metformin.

Most of the common side effects of metformin involve your digestive system. You can minimize your chances of developing side effects by:

Starting with a low dose: It's best to start at a low dose and work up over time to reduce your chances of developing side effects. A typical starting dose is 500 milligrams.

Taking metformin with a meal: Taking metformin with a meal can help reduce your chances of developing an upset stomach or digestive discomfort.

Taking extended-release metformin: You can talk with a doctor to determine whether extended-release metformin might be right for you. This type of metformin releases slowly over time and typically has milder side effects. Be sure to discuss the FDA recall of certain brands of extended-release metformin to ensure that you get a safe version.

Taking pills whole: You should not crush pills. Doing so can mean that your body will absorb them more quickly.

If you develop uncomfortable side effects, contact your prescribing doctor. They may recommend changing your dosage, particularly during times of stress.

It's also a good idea to avoid heavy alcohol use when taking metformin because it can increase your chances of developing lactic acidosis.

Several factors can increase your risk of lactic acidosis while taking metformin. If any of these factors affect you, discuss them with your doctor before taking this medication.

Kidney problems

Your kidneys remove metformin from your body. If your kidneys are not working as they should, you'll have higher metformin levels in your system. This raises your risk of lactic acidosis.

If you have mild or moderate kidney problems, a doctor may start you on a lower metformin dosage.

If you have severe kidney problems or are age 80 or older, metformin may not be right for you. A doctor will likely test your kidney function before you take metformin and then again each year.

Heart problems

If you have diabetes, you are at an increased risk of heart disease. That's because high blood sugar can eventually damage your blood vessels. Therefore, managing your diabetes by taking medications such as metformin may help lower your risk of heart problems.

Studies suggest that metformin may reduce the risk of heart-related death and events among people with type 2 diabetes. It may also lower the risk of death from and reoccurrence of heart failure in people who have already experienced it. However, researchers found these benefits did not occur in people without diabetes.

Liver problems

You should not take metformin if you have severe liver problems.

Your liver clears lactic acid from your body. Severe liver problems could lead to a buildup of lactic acid, which increases your risk of lactic acidosis. Metformin also raises your risk, so taking it is dangerous if you have liver problems.

Alcohol use

Drinking alcohol while taking metformin increases your risk of hypoglycemia. It also raises your risk of lactic acidosis because it increases lactic acid levels in your body.

You should not drink large amounts of alcohol while taking metformin. If you drink alcohol, talk with a doctor about how much alcohol is safe for you to consume while you're taking metformin.

For more information, read about the dangers of drinking with metformin and how alcohol affects diabetes.

Surgical or radiologic procedures

If you plan to have surgery or a radiology procedure that uses iodine contrast, you'll need to stop taking metformin before the procedure. These procedures can slow the removal of metformin from your body, increasing your risk of lactic acidosis. Talk with your doctor about the specific time when you should stop taking metformin.

Your doctor can also tell you when it's safe to resume taking metformin after the procedure. You'll typically get the go-ahead when your kidney function tests have stabilized.

What exactly does metformin do to your body?

Metformin helps lower blood sugar levels by decreasing the amount of glucose produced by the liver and increasing the sensitivity of muscle cells to insulin, allowing them to take up more glucose from the blood.

What is the most serious side effect of metformin?

The most serious side effect of metformin is lactic acidosis, a rare but potentially life threatening condition characterized by the buildup of lactic acid in the bloodstream.

What should you avoid while taking metformin?

Metformin may interact with other medications, including those that help manage blood pressure, seizures, heartburn, and cholesterol.

Talk with your doctor about all the medications you're taking before you begin taking metformin.

While taking metformin, you should avoid excessive alcohol consumption, as it can increase the risk of lactic acidosis.

Why do doctors no longer recommend metformin?

Doctors still recommend metformin as a first-line treatment for type 2 diabetes due to its effectiveness, safety profile, and low cost.

However, in some cases, doctors may consider other medications if metformin is not well-tolerated or if there are specific contraindications, such as kidney impairment.

If you've received a prescription for metformin and you're concerned about its side effects, talk with your doctor. You may want to review this article with them. Be sure to ask any questions you may have, such as:

What side effects should I watch out for?

Am I at high risk for lactic acidosis?

Is there another medication I could take that might cause fewer side effects?

A doctor can answer your questions and work with you to manage any side effects you experience.

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