Long COVID: Diabetes drug metformin could reduce risk

• Researchers evaluated whether a common diabetes medication, metformin, can prevent long COVID.
• They found that metformin can reduce long COVID diagnoses by 40%.
• Further studies are needed to know if these findings apply to the general population.

Long COVID is characterized by ongoing health problems that occur after a COVID-19 diagnosis, and which cannot be explained by other factors.

Symptoms can last for weeks, months, or years. More than 200 symptoms have been identified for long COVID, ranging from fatigue and nausea to memory loss, abdominal pain, and dyspnoea or difficulty breathing.

Several hypotheses for what causes long COVID have been suggested. However, mechanistic studies are at an early stage. Methods for treating or preventing the condition are also early in development.

Currently, the Centers for Disease Control and Prevention (CDC) say that the best way to prevent long COVID is to protect oneself and others from contracting SARS-CoV-2 — the coronavirus that causes COVID-19 — in the first place, for instance by staying up to date with vaccinations.

Methods to prevent long COVID after contracting COVID-19 could improve the quality of life and reduce long-term disability among patients.

Recently, researchers evaluated the potential for three common drugs to prevent long COVID.

They found that patients treated with metformin were significantly less likely than patients treated with a placebo to develop long COVID.

Metformin is a widely available diabetes medication that lowers blood sugar levels by increasing insulin sensitivity.

The new study appears in the journal The Lancet Infectious Diseases.

Metformin linked to lower long COVID incidence

The study was a randomized phase 3 clinical trial. The researchers enrolled 1,126 patients aged between 30 and 85 years who had COVID-19 symptoms and a positive PCR or antigen test result for this viral infection.

While the patients were not hospitalized for COVID-19, they had either overweight or obesity, putting them at a higher risk for developing severe COVID.

The participants were randomized into six groups receiving various combinations of metformin for 14 days, ivermectin for 3 days, fluvoxamine for 14 days, and placebo. Ivermectin is an anti-parasitic drug, and fluvoxamine is used to treat obsessive-compulsive disorder (OCD).

The participants were followed for 10 months. They were asked at several time points over the follow-up period whether they had received a diagnosis of long COVID from a medical provider.

Overall, 8.3% of patients reported a long COVID diagnosis after 300 days of follow-up.

However, just 6.3% of patients that received metformin developed long COVID, compared to 10.4% who received a placebo.

Ivermectin and fluvoxamine did not affect long COVID incidence compared to a placebo.

Underlying mechanisms

Medical News Today spoke with Dr. Mark Guido, an endocrinologist with Novant Health Forsyth Endocrine Consultants in Winston Salem, NC, not involved in the study, about how metformin may have reduced long COVID risk.

“It is hard to say as we still don’t fully understand long COVID, but it could possibly be related to reducing inflammation,” he hypothesized. “Metformin has also been shown to potentially reduce severe COVID and to stop [SARS-CoV-2] virus replication in a lab setting, both of which might also play a role.”

MNT also spoke with Dr. Daniel Kim, a board-certified family physician with Medical Offices of Manhattan, not involved in the study, about how metformin may have reduced long COVID risk.

He agreed that the exact mechanisms of action remain unclear. He also noted, however, that previous studies suggest that metformin has an antiviral effect by inhibiting its replication.

Do the study findings apply to everyone? 

When asked about the study’s limitations, Dr. Guido said: “Since our understanding of long COVID is still evolving, there was no specific diagnostic criteria used to determine who did or did not qualify as having long COVID.”

“The study was also limited to patients who were not already on metformin and were overweight or obese. It is unclear if metformin would have a similar effect on those who are already on metformin for other diseases or who have a normal weight,“ he noted.

“The study also only looked at using metformin to prevent long COVID during a patient’s first COVID infection. It is unclear if metformin would have a similar protective effect on long COVID if a patient had [contracted COVID-19 previously],” he further explained.

Dr. Kim added: “It is also unknown if [the results] can be generalized to early outpatient treatment of covid-19 patients who were previously diagnosed with COVID-19 infection.”

Preventing long COVID

Dr. Guido said that the findings could have huge implications for preventing long COVID.

“Long COVID is quickly becoming a public health crisis. If it can be successfully reduced by an inexpensive, well-tolerated and readily available medication such as metformin, it would have a great benefit on public health in the long run,” he explained.

Dr. Kim agreed that the findings are promising. He noted, however, that further studies are needed to determine whether metformin is similarly effective for the general population.

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