Commonly used diabetes drug leads to lower long-COVID rate

Metformin is the most commonly prescribed drug for type 2 diabetes, prescribed to millions of Americans each year. A new study by researchers at the National Institutes of Health (NIH) published Diabetes care suggests that the drug may reduce the risk of developing Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC) in diabetics.

Metformin lowers blood sugar and is most commonly prescribed as a first-line treatment for type 2 diabetes. The drug is also prescribed off-label for weight loss and other metabolic disorders.

The new findings come from the ongoing RECOVER trial and build on results from a 2023 study that showed metformin reduced the risk of long-COVID disease by 40% in 1,300 overweight or obese adults. These participants were not diabetic.

75,000 adults examined

In the new studyThe authors wanted to see if this effect was also observed in patients taking metformin for diabetes. Previous studies have shown that people with type 2 diabetes are at higher risk of developing long COVID.

The researchers used electronic health records from two databases to compare 75,996 adults who took metformin for their type 2 diabetes with 13,336 records of patients who did not take metformin but took other diabetes medications. They analyzed data from 51,385 adults from the N3C dataset and 37,947 adults from the PCORnet dataset.

The outcomes were a long-COVID diagnosis or death within six months of a confirmed COVID-19 infection, as death precludes a diagnosis of PASC, the authors explained.

Overall, PASC diagnoses were identified in 1.7% of patients in the N3C dataset and 1.3% in the PCORnet set.

The hazard ratios for long COVID or death were different in each database. In N3C, the hazard ratio (HR) for death was 0.79 (95% confidence interval [CI]0.71 to 0.88), indicating a 21% lower long-COVID rate in metformin patients. In the PCORnet group, the HR for death or PASC was 0.87 (95% CI, 0.66 to 1.14), a 13% reduction.

The incidence of Long COVID by diagnosis code was 1.6% metformin versus 2.0% comparator (non-metformin) in the N3C and 2.1% metformin versus 2.5% comparator in the PCORnet. By phenotype, the incidence was 4.8% metformin versus 5.2% comparator in the N3C and 24.7% metformin versus 26.1% comparator in the PCORnet.

Mechanism of action unknown

The mechanism of action of metformin is still unknown.

“In addition to its insulin-sensitizing effects, metformin fundamentally alters metabolism within a cell and may reduce PASC through several mechanisms, including attenuated inflammatory cascade, reduced viral persistence, and suppression of protein translation,” the authors said.

“These data support a modest beneficial effect of metformin on the chronic consequences of SARS-CoV-2 in people with diabetes,” the authors concluded.