Two new reports indicate the drug metformin might lower the risk of death from the COVID-19 virus in people with type 2 diabetes. Unfortunately, the randomized trials that would be necessary to confirm the drug’s potential probably won’t be done.
The first new report, which was published online, was issued by scientists from the Hugh Paul Precision Medicine Institute at the University of Alabama in Birmingham. The leader of the research team was Andrew Crouse, PhD, director of research and operations. They reviewed data from 604 patients who had tested positive for COVID-19 between February 25 and June 22 of this year; 40% of those patients had diabetes. Although the use of insulin was found to have no effect on mortality from the virus, the mortality rate of the metformin-using diabetes patients was 11%, which is just about the same mortality rate as the general population. However, among the diabetes patients who did not use metformin, the mortality rate was 23%.
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As the authors put it, “With 11% being the mortality of metformin users, [this] was comparable to that of the general COVID-19-positive population and dramatically lower than the 23% mortality observed in subjects with diabetes and not on metformin.” The researchers considered the possibility that the patients who were not given metformin had underlying conditions that prevented them from taking it (such as kidney disease and heart failure), but they ruled that out after excluding such patients from their analysis. As they explained, “This makes any potential confounding effects from skewing metformin users towards healthier subjects without these additional comorbidities very unlikely.”
The second look at the possible use of metformin in the treatment of COVID-19 appeared in the journal Diabetes & Metabolism. Written by André J. Scheen, MD, of Liege University in Belgium, it summarized data from four earlier observational studies. A French study of over 1,300 patients with diabetes showed significant improvement with metformin, and two smaller studies reported similar results. Interestingly, the largest study, which was from the United States and which analyzed data from over 6,000 patients hospitalized with COVID-19, found a reduction in mortality among female patients but not male patients. All together, the four studies reported a 25% reduction in death from COVID-19 in metformin users.
Scheen also reported on several proposed theoretical explanations for metformin’s apparent benefit for COVID-19 patients with diabetes. Among them were that metformin reduces inflammation, that it inhibits virus penetration, and that it helps affected patients with blood sugar control, weight and insulin resistance. As he wrote, “Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects, it may be speculated that [metformin] might positively influence the prognosis of patients with [type 2 diabetes] hospitalized for Covid-19.” Furthermore, he wrote, “There are at least no negative safety indications, so there is no reason to stop metformin therapy during COVID-19 infection except in cases of severe gastrointestinal symptoms, hypoxia and/or multiple organ failure.”
Despite the encouraging reports about the benefits of metformin in diabetes patients with COVID-19, Scheen pointed out that the reports he surveyed in his paper are observational studies and therefore “caution is required before drawing any firm conclusions in the absence of randomized controlled trials.” Randomized controlled trials, or RCTs, are the standard procedures for testing medications, but they are costly and time-consuming, which is why Scheen wrote, “Such trials are almost impossible in the context of COVID-19.”