With the association between diabetes and more severe COVID-19 infection now well established, there is much interest in studying whether any particular type of diabetes medication may protect against having a more severe infection.  As a commonly prescribed and first line medication for type 2 diabetes, the question has been asked whether being on metformin prior to getting COVID-19 could be protective.


A recent study looked at health records of over 25,000 patients at a US hospital who had been tested for COVID-19, looking for risk factors associated with an increased risk of death from the virus.  In this population, 604 people tested positive for the coronavirus, and 239 of these had diabetes. They found that diabetes itself was associated with a 3.6x higher risk of death from COVID-19 (consistent with existing data).  Interestingly, they found that metformin treatment prior to the diagnosis of COVID-19 was independently associated with a 67% reduction in mortality in people with diabetes. This was after controlling for age, gender, ethnicity, obesity, insulin use prior to COVID diagnosis, and hypertension.  Thus, while the numbers of patients were small, these data suggest that while diabetes is a risk factor for severe COVID, being on metformin prior to contracting COVID-19 appeared to reduce this risk.


However, as recently discussed in an excellent review by Dr Dan Drucker in the journal Cell Metabolism, the data on metformin are not entirely consistent.  Another retrospective study of health care claims data found that metformin use was associated with a reduction in mortality in women, but not in men.   A third study did not show a difference in mortality at 28 days of hospitalization.


How could metformin protect against severe COVID infection?  Interestingly, metformin has been shown to have anti-inflammatory effect, and may help to prevent thrombosis (blood clots).  As severe COVID-19 infection is characterized by an excessive inflammatory response called cytokine storm, often with blood clotting (called disseminated intravascular coagulation), it is possible that metformin may help to control this response.


As noted by Dr Drucker, inferring real associations between glucose lowering medications and COVID-19 outcomes is difficult, because of many confounding factors that can be difficult to control for.  Because metformin is usually prescribed first in new or easy to control type 2 diabetes, these patients likely had diabetes for a shorter period of time, and were probably less likely to carry complications of diabetes that can further increase risk of poor COVID outcomes (eg heart or kidney disease).


BOTTOM LINE: While some data suggest that metformin may reduce the risk of severe COVID outcomes in people with type 2 diabetes, we will probably never know for sure. What we do know is that metformin is an excellent medication for treatment of type 2 diabetes and should be considered as a first-line treatment strategy for type 2 diabetes.


PS – While we focused on metformin today, note that Dr Drucker’s excellent review includes a great discussion of other diabetes medications, as well as many other aspects of diabetes, obesity, and COVID-19 infection.


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