For months now, it’s been increasingly clear that people with diabetes are at greater risk for severe disease and complications if they develop COVID-19. While researchers are still trying to figure out all the mechanisms that explain this link, it’s been shown that elevated blood glucose levels affect how the immune system operates — often leading to higher levels of inflammatory markers in the blood of people who develop COVID-19, as seen in a May 2020 study.
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This study also found that in people with diabetes who were hospitalized for COVID-19, those with higher blood glucose at the time of admission experienced more severe disease and worse outcomes during their hospital stay. Within this group of people with initially high blood glucose, those who received insulin during their hospital stay ended up with a lower risk of complications from COVID-19.
But insulin isn’t the only diabetes treatment that may be helpful in lowering the risk of complications from COVID-19, including death. A recent study by researchers at the University of Minnesota — still not peer-reviewed or officially published — found that taking the drug metformin was associated with a significantly lower risk of death from COVID-19 among women hospitalized for the infection.
The new study looked at insurance claims to identify people hospitalized for COVID-19, in all 50 US states, with type 2 diabetes or obesity. Researchers then looked for people within this group who had at least 90 days of metformin insurance claims within the last year, nearly all of whom had type 2 diabetes. The researchers then compared this smaller group of people taking metformin with the larger group of hospitalized people.
Overall, the study included 6,256 people with type 2 diabetes or obesity who were hospitalized for COVID-19. Their average age was 75, and 52.8% were women. Within this larger group, 2,333 people had a prescription for metformin. Among women only, taking metformin was associated with a 24% lower risk of death during hospitalization, based on a common way of calculating this risk. The researchers noted that in past studies, metformin has been shown to lower an inflammatory protein called TNF-alpha in women, but not by nearly as much in men.
It’s possible that this effect accounts for the difference in death risk from COVID-19 seen in women in this study.
To further back up the connection between TNF-alpha and death risk from COVID-19, the researchers looked at prescription claims within the larger hospitalized group for drugs called TNF inhibitors, which are used to treat certain inflammatory diseases and directly reduce levels of TNF-alpha. Those who took TNF inhibitors, a total of 38 people, were 81% less likely to die while hospitalized than the larger group of people with type 2 diabetes or obesity.
It’s important to note that while these findings show a significantly lower risk of death in women who took metformin, the study was observational — meaning that it only looked at different groups of people after the fact, instead of comparing treatments from the start. Since people who take metformin may be different in many ways from people with type 2 diabetes or obesity who don’t take the drug, this means there could be factors other than the drug itself that account for some or all of the lower death risk seen in the metformin group.
More studies, the researchers write, are needed to confirm that metformin actually offers a protective effect against death from COVID-19, and that it does so by reducing TNF-alpha. Of course, if TNF inhibitors actually lower the risk of death from COVID-19 as dramatically as this study suggests, it may be more worthwhile to investigate the possibility of directly reducing or blocking TNF-alpha, rather than using metformin to do this indirectly in women only.
Want to learn more about coronavirus and diabetes? Read “Coronavirus and Diabetes: What You Need to Know,” “Healthy Eating During Hard Times” and “Avoiding Coronavirus With Diabetes: Stock Up and Stay Home, CDC Says.”