FollowThe scientists on Monday found a mixed safety report of a diabetes pills as the studies showed them as not a potent accelerator of heart attacks but simultaneously its link to heart failure was not denied in the report.
The studies presented on 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 on Monday in the New England Journal of Medicine.
Two studies were conducted independently of each other to verify the safety standards of the drugs. 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. BMY -0.24% and AstraZeneca AZN.LN +0.08% 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. 4502.TO +1.12% and Sanofi SA’s SAN.FR +2.08% Nesina—in nearly 5,400 patients for an average of 18 months.
Both the studies 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.
“It is a little bit concerning,” said Dr. Christopher Grainger of Duke University Medical Center, who was not involved in the research. “I’m sure the FDA (U.S. Food and Drug Administration) will want to know more about it.”
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.
Drugs like Onglyza and Nesina work by inhibiting dipeptidyl peptidase-4, or DPP-4, to enhance the body’s ability to lower elevated levels of blood sugar.
DDP-4s are not the most powerful agents for lowering blood sugar levels but they are well tolerated and have proved an attractive option for doctors looking for new oral drugs.
The DPP-4 market is dominated by Merck’s Januvia, which has annual sales of around $5 billion, including a related combination treatment called Janumet. But growth of the class has slowed this year, partly on concerns over pancreatic safety.
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.
