Metformin is the most common type 2 diabetes drug prescribed to millions of American each year, and a new study from researchers at the National Institutes of Health (NIH) published in Diabetes Care suggests the drug can lower 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 also is prescribed off-label for weight loss and other metabolic conditions.
The new findings come from the ongoing RECOVER trial and build on results seen in a 2023 trial, which showed metformin cuts the risk of long COVID by 40% in 1,300 adults who were overweight or obesity. Those participants were not diabetic.
75,000 adults studied
In the new study, the authors wanted to see if that effect was still seen in those taking metformin for diabetes. Previous studies have shown that people with type 2 diabetes are more at risk for developing long COVID
The investigators used electronic health records from two databases to compare 75,996 adults taking metformin for their type 2 diabetes to 13,336 records from patients who were not taking metformin but were using other types of diabetes medicine. They analyzed data from 51,385 adults from the N3C data set and 37,947 adults from the PCORnet data set.
Outcomes were long COVID diagnosis or death within 6 months of a confirmed COVID-19 infection, because death precludes a diagnosis of PASC, the authors explained.
Overall, PASC diagnoses were seen in 1.7% of patients in the N3C of the data set 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), or 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 PCORnet. By phenotype, incidence was 4.8% metformin and 5.2% comparator in the N3C and 24.7% metformin versus 26.1% comparator in PCORnet.
Mechanism of action unknown
Metformin's mechanism of action is still unknown.
"In addition to insulin-sensitizing effects, metformin fundamentally changes the metabolism within a cell and could decrease PASC via several mechanisms, including an attenuated inflammatory cascade, decreased viral persistence, and suppression of protein translation," the authors said.
"These data support a mildly beneficial role of metformin on chronic SARS-CoV-2 outcomes in people with diabetes," the authors concluded.
