By Deborah J Nelson and Chad Terhune
(Reuters - AstraZeneca Plc is testing one of its diabetes drugs as a treatment for COVID-19, even as doctors are advising diabetes patients infected by the coronavirus to stop taking the medicine and others like it because of a potentially dangerous side effect.
Dapagliflozin, sold under the brand name Farxiga, belongs to a class of widely prescribed diabetes medicines known as SGLT2 inhibitors, which help control blood glucose levels by increasing the amount of sugar excreted through urine.
The drug also has been shown to reduce the risk of death and hospitalization from heart failure and slow progression of kidney failure. The study will test whether its protective effects extend to COVID-19, the disease caused by the new coronavirus that can lead to heart and kidney complications.
The trial of 900 hospitalized patients, dubbed DARE-19, will test Farxiga against a placebo with results expected by December. The international study began in April.
"While we don't fully understand the mechanisms of how these medications protect the heart and kidneys, we know that they do," said Dr. Mikhail Kosiborod, a cardiologist at Saint Luke’s Mid America Heart Institute in Kansas City who is leading the COVID-19 trial.
"We know that they do that in patient populations that have cardio metabolic disease - exactly the same patient population that are at such high risk in the setting of COVID-19," he added.
If successful, doctors will have to weigh the benefits to COVID-19 patients against the risk of diabetic ketoacidosis, a type of blood poisoning that can lead to coma or death that has been linked to SGLT2 inhibitors.
Gilead Sciences Inc's remdesivir is the only treatment that has demonstrated benefit for COVID-19 patients in a large, placebo-controlled trial. Drugmakers are testing dozens of additional therapies to help mitigate a pandemic that has killed more than 350,000 people worldwide.
'SOMETHING WE CAN PREVENT'
Although rare, diabetic ketoacidosis is more likely to occur during a serious illness. That puts COVID-19 patients who regularly take the drug at a higher risk.
Nearly 30% of people hospitalized with COVID-19 had diabetes, according to a study posted on April 17 by the U.S. Centers for Disease Control and Prevention. As a result, many doctors are taking diabetes patients off that class of medications out of an abundance of caution during the pandemic.
"I've already seen a patient with type 2 diabetes on one of these drugs develop ketoacidosis with a COVID-19 infection," said Dr. Anne Peters, director of the clinical diabetes program at the University of Southern California. She is advising patients who test positive to stop taking the drugs to reduce the risk of ketoacidosis. "It’s something that we can prevent if people know about it."
The other SGLT2s are Johnson & Johnson's Invokana and Jardiance, sold by Eli Lilly and Co and Boehringer Ingelheim.
Dr. Robert Eckel, president of medicine and science at the American Diabetes Association, said the organization has not made a formal recommendation. But he and other specialists on ADA webinars "have recommended against the use of SGLT2 inhibitors in hospitalized patients with COVID-19 infection."
AstraZeneca, which is also testing a high-profile vaccine to prevent infection by the coronavirus with the University of Oxford, said "there currently isn't data on the use of dapagliflozin in patients being treated for COVID-19." The DARE-19 trial will determine if there are benefits, the British drugmaker said.
Farxiga earlier this month won additional U.S. approval to treat a common type of heart failure, even for those without diabetes, after studies showed it reduced the risk of death and hospitalizations.
The new study will test whether the drug reduces the risk of death and complications among COVID-19 patients.
Patients with type 2 diabetes will be allowed to enroll as long as they have not had a recent episode of ketoacidosis. They will be closely monitored, Kosiborod said, adding Farxiga should not be used to treat COVID-19 outside a tightly controlled clinical setting.
Boehringer Ingelheim and Eli Lilly said in a statement they are "carefully assessing" their products as potential COVID-19 treatments, while noting the Jardiance label warns acute illness heightens the ketoacidosis risk.
J&J said it has no plans to test Invokana for COVID-19.
(Reporting by Chad Terhune in Los Angeles and Deborah Nelson in Maryland; Editing by Bill Berkrot)