Can drugs used to treat diabetes help fight the COVID-19 pandemic? A growing number of researchers think so and are actively pursuing research into the matter.
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COVID-19, SGLT2 inhibitors, and GLP-1 receptor agonists
There are good reasons to think the medications might be effective in COVID treatment. At a recent Heart in Diabetes (virtual) meeting, Mikhail Kosiborod, MD, cardiologist at Saint Luke’s Mid America Heart Institute and Vice President of Research at Saint Luke’s Health System, pointed out that COVID-19 is not just a viral disease — it’s also both a systemic disease (that is, it affects the entire body, not just a part of it) and a cardiometabolic disease. (A cardiometabolic disease is one that combines cardiovascular risk with metabolic problems, such as insulin resistance and diabetes. Cardiometabolic diseases tend to share common risk factors).
COVID-19 strikes the same body systems that cardiometabolic disease and diabetes do, which might explain why the virus often affects people with diabetes and other cardiometabolic diseases more severely. As Mansoor Husain, MD, professor of medicine at the University of Toronto and executive director of the Ted Rogers Centre for Heart Research in Toronto, said at the Heart in Diabetes meeting, “This is a field that’s rapidly moving. Our understanding of Covid-19 remains quite limited. Experience and expertise are in short supply, of short duration and fragmented.” Two classes of medications are of special interest in the COVID war: glucagon-like peptide 1 (GLP-1) receptor agonists and SGLT2 inhibitors.
According to M. Regina Castro, MD, of the Mayo Clinic, GLP-1 receptor agonist diabetes drugs “mimic the action of a hormone called glucagon-like peptide 1. When blood sugar levels start to rise after someone eats, these drugs stimulate the body to secrete more insulin. The extra insulin helps lower blood sugar levels.” Well-known GLP-1 receptor agonist drugs include dulaglutide (brand name Trulicity), exenatide (Byetta, Bydureon), semaglutide (Ozempic), semaglutide (Rybelsus), lixisenatide (Adlyxin) and liraglutide (Victoza). All, with the exception of Rybelsus, are administered through injection. At the Heart in Diabetes meeting, Husain proposed that GLP-1 receptor agonist diabetes drugs might be used to treat the COVID-caused vascular complications that excessively affect diabetes patients. As he observed, “They prevent vascular inflammation, they promote vasodilation, they prevent smooth muscle cell activation and platelet aggregation.” A Canadian initiative called the SEMPATICO trial has very recently been established to test the effectiveness of semaglutide in lowering the death rate among certain COVID patients, as well as their need for cardiorespiratory support, such as a ventilator. The trial patients are at higher risk — those who are older, or obese, or have high blood pressure or have heart trouble.
The other diabetes drugs COVID researchers are seriously looking at are the sodium glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors inhibit the proteins in the kidneys that promote returning glucose into the blood, which causes blood sugar to discharge into the urine, thereby lowering the amount of glucose in the blood. Four SGLT2 inhibitors are currently available: canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance) and ertugliflozin (Steglatro). The main reason researchers think these medications might help COVID patients is because they help many of the processes damaged by viruses. According to Husain, “We already know that SGLT2’s provide organ protection.” They can reduce inflammation, lower insulin levels, and inhibit the extraction of energy from blood sugar (glycolysis). Studies have previously demonstrated that they are of value in treating heart failure and kidney disease, as well as diabetes.
Some researchers have wondered if they work quickly enough to be of use in treating viral disease, but Husain says that studies have shown that they can bring benefits within days. Kosiborod is leading a research team that is conducting a trial called DARE-19. The international, randomized, double-blind, placebo-controlled trial, sponsored by the pharmaceutical firm AstraZeneca, has enrolled about 900 patients to study the potential of dapagliflozin in safely and effectively treating people with COVID who are at risk of serious complications, such as organ failure, heart arrhythmia and respiratory difficulty requiring the use of ventilators. Kosiborod says, “Dapagliflozin has demonstrated cardio and renal protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and chronic kidney disease. Patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications. Through DARE-19, we hope to decrease the severity of illness and prevent cardiovascular, respiratory and kidney decompensation, which are common in patients with COVID-19.”
Want to learn more about coronavirus and diabetes? Read “Coronavirus and Diabetes: What You Need to Know,” “Healthy Eating During Hard Times” and “COVID-19: Staying Safe at Work.”