BY AMERICAN HEART ASSOCIATION NEWS
Editor’s note: This is one in a 10-part series of the top medical research advances as determined by American Heart Association volunteer and staff leaders.
After decades of coming up empty in the search for a diabetes drug that could lower heart risks, researchers believe they have found a medication that does just that. A new study with the drug Jardiance is the first to reduce deaths from heart complications.
In the study, those who added Jardiance to their Type 2 diabetes treatment regimen had a 38 percent lower risk of dying from cardiovascular causes after about three years. Patients were also 35 percent less likely to be hospitalized for heart failure.
The results surprised doctors who long have been frustrated by trials showing that lowering patients’ blood sugar had no clear heart benefits.
“It’s a door that’s been cracked for some time in terms of convincing evidence that a single intervention to lower glucose reduces cardiac events,” said endocrinologist Robert Eckel, M.D., a professor of medicine at the University of Colorado who was not involved in the study.
Jardiance, known generically as empagliflozin, was approved by the Food and Drug Administration in August 2014. It’s a member of a drug class called SGLT2 inhibitors. Two other SGLT2 inhibitors – Farxiga and Invokana – are also approved. They work by excreting glucose, or blood sugar, in the urine. Trials are under way to test whether Farxiga and Invokana offer the same benefits.
Nearly 22 million Americans have been diagnosed with Type 2 diabetes, the nation’s seventh-leading cause of death, according to the Centers for Disease Control and Prevention.
The disease causes blood sugar levels to rise too high and can lead to serious health problems such as nerve and kidney damage, blindness and cardiovascular diseases. Heart disease kills at least two-thirds of older diabetics and stroke kills one in six, according to the American Heart Association.
The global study, called EMPA-REG, included 7,020 Type 2 diabetes patients who already had cardiovascular diseases and were therefore at high risk for heart attacks and strokes. Participants took standard drugs to treat diabetes, high cholesterol and high blood pressure, plus either Jardiance or a placebo.
Although those taking Jardiance were only slightly less likely to have a nonfatal heart attack and slightly more likely to have a nonfatal stroke, the differences were not statistically significant. However, when deaths from heart attack, heart failure and stroke were analyzed together, the benefits became clear.
In all, 3.7 percent of patients taking Jardiance died from cardiovascular causes, compared with 5.9 percent taking the placebo. In addition, the risk of dying from any cause fell by almost a third, from 8.3 percent in the placebo group to 5.7 percent in the Jardiance group.
The lower dose of the daily pill proved just as effective as the higher dose, although both doses increased the risk of genital infections. The FDA on Friday issued a warning that SGLT2 inhibitors can cause serious urinary tract infections and a condition called ketoacidosis, in which the blood becomes too acidic.
Yet given the new results, Jardiance could become the go-to drug after metformin, the recommended first drug of choice, Eckel said.
“The question has been, after metformin, where do we go? There are 13 other classes of diabetes drugs to choose from,” said Eckel, a past AHA president. Eckel helped write the AHA and American Diabetes Association recommendations for preventing cardiovascular diseases in Type 2 diabetics.
“Now with the cardiovascular disease benefit, I think we’re going to see empagliflozin be a second-line drug for many people,” he said.
However, Silvio Inzucchi, M.D., director of the Yale Diabetes Center and senior author of the study, cautioned that the findings can only be applied to patients like those in the trial – Type 2 diabetics who already have cardiovascular disease. Inzucchi was also a member of the AHA/ADA writing group.
With a wholesale price of $411 for a month’s supply, Jardiance is one of the more expensive diabetes drugs. The other two SGLT2 inhibitors carry a similar price tag.
Researchers admit they aren’t sure exactly how the glucose-lowering drug is reducing cardiovascular deaths. It may come from Jardiance’s diuretic affect or its ability to lower weight and blood pressure, Inzucchi said.
“Once we find the mechanism,” he said, “there will be interest in developing more drugs to both help lower glucose and prevent cardiovascular deaths.”