Metformin is the most common type 2 diabetes medication prescribed to millions of Americans each year, according to a new study by researchers at the National Institutes of Health (NIH). Diabetes Care The findings suggest that the drug could reduce the risk of developing long COVID, or persistent acute sequelae of SARS-CoV-2 infection (PASC), in diabetic patients.
Metformin lowers blood sugar levels 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 to treat other metabolic diseases.
The new findings come from the ongoing RECOVER trial. 2023 TrialsThe study showed that metformin reduced the risk of long COVID by 40% in 1,300 adults who were overweight or obese. These participants did not have diabetes.
75,000 adults surveyed
The authors wanted to see whether the benefit also appeared in people taking the diabetes drug metformin, as previous studies have shown that people with type 2 diabetes are at higher risk of developing long-term COVID-19.
Using electronic health records from the two databases, the researchers compared records of 75,996 adults who were taking metformin to treat type 2 diabetes with 13,336 patients who were not taking metformin but were taking other types of diabetes medications. The researchers analyzed data from 51,385 adults from the N3C data set and 37,947 adults from the PCORnet data set.
The outcome was defined as long-term COVID diagnosis or death within six months of confirmed COVID-19 infection, because death precludes a diagnosis of PASC, the authors explained.
Overall, PASC diagnosis was present in 1.7% of patients in the N3C dataset and 1.3% in the PCORnet set.
The hazard ratios for long COVID or death varied across databases. In N3C, the hazard ratio (HR) for death was 0.79 (95% CI 0.01–0.25). [CI]0.71-0.88), indicating a 21% lower incidence of long COVID in metformin patients. In the PCORnet group, the HR for death or PASC was 0.87 (95% CI, 0.66-1.14), a 13% reduction.
Incidence of Long COVID by diagnosis code was 1.6% metformin vs. 2.0% comparator (non-metformin) in N3C and 2.1% metformin vs. 2.5% comparator in PCORnet. By phenotype, it was 4.8% metformin vs. 5.2% comparator in N3C and 24.7% metformin vs. 26.1% comparator in PCORnet.
The mechanism of action is unknown
The mechanism of action of metformin remains unclear.
“In addition to its effect of enhancing insulin sensitivity, metformin fundamentally alters intracellular metabolism and may reduce PASC through several mechanisms, including attenuating the inflammatory cascade, reducing viral persistence and inhibiting protein translation,” the authors write.
“These data support a modest beneficial role of metformin on chronic SARS-CoV-2 outcomes in patients with diabetes,” the authors concluded.