For the study, published in May 2020 in the American Journal of Tropical Medicine and Hygiene, researchers studied the health outcomes of 283 people hospitalized for COVID-19 in Wuhan, China, who all had diabetes, according to the paper. The analysis included 104 participants taking metformin and 179 patients who didn’t take this drug. Metformin is commonly prescribed to people with type 2 diabetes to help lower their A1C, a three-month average of blood sugar levels. The two groups were similar in terms of their age, the number of chronic illnesses they had in addition to diabetes, the severity of COVID-19 when they arrived at the hospital, and the amount of oxygen support they required. While the patients on metformin had slightly worse blood sugar control at the time of hospital admission, both groups had similar blood sugar levels during their hospital stay. Despite that, their death rates were distinct. Only 2.9 percent of participants on metformin died during their hospital stay, compared with 12.3 percent of those who didn’t take metformin. “Findings of the current study are of tremendous importance because many doctors are stopping metformin in COVID patients,” says Anoop Misra, MD, the chairman of the Fortis-C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology in New Delhi. “In view of the possible survival benefit, we should continue it.” Dr. Misra wasn’t involved in the study. RELATED: 10 Diabetes Care Tips During the COVID-19 Pandemic
Why Some Doctors Stop Metformin Use in People With COVID-19
Although proper blood sugar control can help reduce the severity of COVID-19, some doctors are halting metformin therapy in people hospitalized with the disease because of concerns about a rare but dangerous side effect, Misra says. In some instances, particularly when people with diabetes who are hospitalized with COVID-19 are dehydrated or have reduced kidney function, metformin can contribute to the onset of a dangerous process called ketoacidosis, according to the American Heart Association. Diabetic ketoacidosis is life-threatening, and can happen when the body doesn’t have enough insulin to convert blood sugar into energy and instead burns fat for fuel, a process that releases substances known as ketones into the blood. When ketones accumulate in the bloodstream, the blood becomes acidic and poisonous. Another potential issue with metformin is the way it may interact with contrast dye patients sometimes drink to enhance imaging that doctors use to diagnose and treat COVID-19. The mix of metformin and contrast dye may accelerate kidney failure, according to the AHA. RELATED: What’s the Difference Between Ketosis and Diabetic Ketoacidosis?
How Metformin May Help Fight COVID-19 in People With Type 2 Diabetes
People with diabetes are more prone to serious complications from infections when their blood sugar levels are too high, Misra says. But having well-controlled blood sugar, whether thanks to metformin or other approaches, can improve prognoses, he adds. Metformin in particular may have properties that make it well suited to reducing the severity of COVID-19 in people with diabetes. People with severe COVID-19 can have an excess of immune system proteins called cytokines in their bloodstream. These proteins are thought to accumulate as a result of what’s known as a cytokine storm, when the body attacks its own tissues in addition to the infection it’s trying to fight. “Metformin may decrease the surge of harmful poisonous substances in blood termed as inflammatory cytokines,” Misra says. When cytokine storms don’t develop, the risk of dying from COVID-19 may decrease. RELATED: What You Need to Know About COVID-19 When Living With a Compromised Immune System More studies are needed, but the way metformin works in the body to regulate blood sugar may also help block viruses like the one that causes the novel coronavirus from entering the body and spreading, says Prasad Katulanda, MD, an endocrinologist and senior lecturer at the University of Colombo in Sri Lanka, who wasn’t involved in the study. Metformin activates an enzyme in the body known as AMP-activated protein kinase (AMPK) to boost glucose metabolism. This process is also thought to block the activity the so-called angiotensin-converting enzyme 2 (ACE2) receptor, a protein that serves as a gateway for the coronavirus to enter and infect other cells, Dr. Katulanda says. “Therefore, it is potentially possible that metformin has other mechanisms through which it has protective effects in COVID infection,” Katulanda says. RELATED: What Are the Possible Complications of Type 2 Diabetes and How Can You Avoid Them?
Other Studies Suggest Metformin May Lessen the Severity of Respiratory Illnesses
Previous research has consistently found that people with diabetes who take metformin have a lower risk of pulmonary diseases including acute asthma attacks, chronic obstructive pulmonary disease (COPD), pneumonia, and tuberculosis, says Awadhesh Kumar Singh, MD, a senior consultant in diabetes and endocrinology at G.D. Hospital and Diabetes Institute in Kolkata, India, who wasn’t involved in the current study. For example, a study consisting of participants with both diabetes and COPD published in April 2019 in Respiratory Research found that individuals taking metformin had a 54 percent lower death rate over two years compared with individuals who didn’t take this drug. Yet researchers simply observed an association between taking metformin and a lower risk of premature death; the researchers concluded that randomized studies are needed to confirm a causal relationship. In addition, some studies have suggested that people with diabetes hospitalized with infections including pneumonia and sepsis have lower mortality rates when they take metformin than when they don’t, Dr. Singh adds. Another study, published in November 2018 in the European Respiratory Journal, found that people with a history of diabetes hospitalized with pneumonia had 20 percent lower 30-day mortality rates when they took metformin than when they didn’t take this medicine. Yet this study was also only observational, and more research is needed. RELATED: Obesity May Increase the Risk for COVID-19 Complications
What We Still Don’t Know About Metformin and COVID-19
Like much of the other research, the current study wasn’t a controlled experiment that randomly assigned some people to take metformin and others to take a placebo — in other words, a randomized controlled trial, which is the gold standard for research because it shows a cause-and-effect relationship between two factors. So it’s not possible to know whether the survival benefit associated with metformin was directly caused by the drug or whether some other factors not measured in the study may have played a role. “Urgent randomized trials are needed to address this question scientifically,” says Dr. Katulanda. “At this point it is difficult to say whether metformin provides benefit in patients with diabetes and COVID-19 due to blood glucose control or other mechanisms. “The take-home message is that people with diabetes should continue metformin amid the [COVID-19 pandemic]," Katulanda says. If they do develop COVID-19, then doctors need to consider whether halting treatment is necessary on a case-by-case basis, Katulanda advises. RELATED: 10 Misconceptions About the Coronavirus
