New Diabetes Drugs Don’t Raise Heart-Attack Risk

Two large studies to be presented at an international cardiology meeting offer some reassurance to doctors and patients, though one showed bump in heart-failure hospitalizations.

AMSTERDAM—A new class of diabetes drug doesn’t appear to increase risk of heart attack, according to two large studies, offering some reassurance to doctors and patients who had concerns about possible negative effects on the heart.

But there was a signal in one of the trials—which are being presented at an international cardiology meeting Monday—that the drug may increase patients’ risk of hospitalizations for heart failure.

The findings also raise questions about whether drugs that only lower blood sugar, without addressing cholesterol, blood pressure or lifestyle factors, are enough to improve heart health. Previous small trials had suggested a possible benefit from lowering blood sugar.

Scrutiny about diabetes drugs’ possible deleterious cardiovascular effects arose in recent years after a controversy about whether a diabetes medicine of a different class, GlaxoSmithKline PLC’s Avandia, was linked to an increase in heart attack risk in some patients.

In 2008, the U.S. Food and Drug Administration issued guidance that drug makers needed to demonstrate that new diabetes drugs wouldn’t lead to an “unacceptable increase in cardiovascular risk.”

In 2010, Avandia was removed from the market in Europe and its use was restricted in the U.S.

But in June, a Duke University study was published suggesting there was no increase in cardiovascular events with Avandia, and an expert committee advised the FDA to ease restrictions on use.

The studies presented Monday at the European Society of Cardiology Congress investigated a newer class of drugs known as DPP-4 inhibitors, which are supposed to help bring diabetics’ blood sugar into the normal range.

Both studies were also published Monday in the New England Journal of Medicine.

One of the trials, known as Savor Timi-53, was a 16,492-patient study on the medication saxagliptin, marketed by Bristol-Myers Squibb Co. and AstraZeneca PLC as Onglyza.

Patients with Type 2 diabetes and who had a history of or were at risk for cardiovascular events were randomized to the medicine or a placebo, in addition to other standard treatment for their diseases.

They were followed for an average of two years.

The other study, called Examine, was a randomized study of alogliptin—Takeda Pharmaceutical Co. and Sanofi SA’s Nesina—in nearly 5,400 patients for an average of 18 months.

The studies, conducted independently of each other, found similar outcomes on the main endpoint of heart attack: The gliptins didn’t increase heart attack risk compared with placebo but also didn’t lower risk.

However, there was a statistically significant difference in heart-failure hospitalizations with Onglyza: 3.5% for the group taking the medicine compared with 2.8% for the control group.

“I think what we have provided in this trial is a great deal of clarity with respect to heart-attack risk,” said Deepak Bhatt, a senior physician at the Brigham & Women’s Hospital in Boston, who will be presenting the Savor data on Monday. “But this heart-failure finding was unexpected. For that reason, it’s important to be a little bit cautious in interpreting it.”

The finding needs further examination to verify the findings and understand which patients might be susceptible to heart failure, according to Dr. Bhatt.

“What we need to do and, in fact what we’re doing, is really trying to drill down on that and see exactly who might be at risk for heart failure,” said Dr. Bhatt, also chief of cardiology at the VA Boston Healthcare.

Overall, however, experts who weren’t involved in the study said the data largely put to rest concerns about the possible heart-attack risk with DPP-4 inhibitors.

“I personally feel a certain amount of reassurance,” said Anthony DeMaria, a professor of medicine at the University of California, San Diego and editor in chief of the Journal of the American College of Cardiology. “Gliptins can be incorporated into overall diabetes treatment without excessive concern about cardiac effects.”

It remains a question whether diabetes drugs that lower blood sugar can benefit the heart. Some experts said they were discouraged by Monday’s findings that suggest DPP-4 inhibitors don’t decrease heart-attack risk while others said they had never expected a benefit because a multipronged approach is necessary.

The DPP-4 inhibitors tend to be mild in their effect but well-tolerated, but it is “not very logical” to think that lowering blood glucose alone would translate into reduction in heart-attack risk, said Heinz Drexel, chairman of the department of medicine and cardiology at Feldkirch Hospital in Austria and president of the Austrian Diabetes Association.

He wasn’t involved in these trials but has been an investigator on various clinical trials of diabetes drugs.

“Glucose-lowering should be accompanied by cholesterol-lowering through statins and by blood-pressure control,” said Dr. Drexel.

In addition, these latest findings suggest that the FDA needs to think about a new way of assessing diabetes drugs, according to Sanjay Kaul, a cardiologist at Cedars-Sinai Medical Center in Los Angeles, who wrote an accompanying editorial in Monday’s New England Journal of Medicine.

Currently a blood-based marker of glucose control called HbA1c, which serves as a proxy for how well the diabetes is controlled, is used as a primary outcome measure on which approvals are based.

But “it is time for the FDA to consider a patient-oriented clinical outcome of benefit,” such as prevention of kidney failure or blindness, said Dr. Kaul in an email.

“While it is reassuring that evidence does not suggest [cardiovascular concerns], it is disappointing that none of these therapies provide CV benefit,” said Dr. Kaul.

Source The Wall Street Journal