Dichotomy #1

Metformin in Diabetes and COVID-19: Boon or Bane?

Metformin is one of those drugs that is older than dirt and still quite useful. It has helpful effects in obesity. It’s a mainstay of drug therapy for type 2 diabetes. But metformin presents a bit of a puzzle in patients with diabetes who become infected with COVID-19. Some signs point to a benefit for patients who have been taking metformin before they get COVID-19. Other observations point to a potential for harm if the disease becomes severe.

All of this is from observational studies, so the answers are still murky. It’s a classic tale of how difficult it can be to weigh risks and benefits.

A Survival Benefit

Carolyn Bramante et al recently published a large observational study of metformin use and mortality in COVID-19 patients. They examined medical claims records for 6,256 patients in the United Health Group database. These were patients who had type 2 diabetes and were admitted to the hospital for COVID-19. They found an approximate 22 percent reduction in mortality risk with prior use of metformin – but only in women. For men, it appeared to make no difference.

Of course, this is an observational study. So we need prospective research to confirm if there really is a benefit. Bramante and her colleagues are ready to start enrolling patients in such a study.

Problems in the Hospital

On the risk side of the equation, however, there’s good data to suggest that metformin use can be a problem after a patient is hospitalized with severe COVID-19. In Cell Metabolism, Cheng et al published a study that documents an association between metformin use and acidosis for this group of patients. Their cohort included 2.563 patients with type 2 diabetes who were hospitalized for COVID-19.

They found that the risk of acidosis more than doubled for these patients  if they had been taking metformin. This can be a serious problem for patients with diabetes. But in this analysis, metformin use did not have an adverse effect on mortality. In fact, they found metformin associated with less heart failure and inflammation.

Cautious Advice and Further Studies

In the face of all this, the consensus is for caution. One set of guidelines recommends discontinuing metformin if a patient develops severe symptoms of COVID-19. Meanwhile, we have speculation that metformin might be a cheap and effective treatment for patients with both COVID and type 2 diabetes.

All of this is interesting and metformin is certainly useful in the right situation. For example, it’s clearly helpful for glycemic control and that’s important for good outcomes with COVD-19. But this is not the first and it won’t be the last time people make wonder drug claims about metformin. So we advise caution. Having inexpensive options for treating a serious disease is great – only if they work safely.

We still have much to learn.

Click here for the Bramante study and here for the Cheng study. For further perspective, this commentary is quite helpful.

Dichotomy #1, photograph © Brett Jordan / flickr

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December 19, 2020