Diabetes drug trials answer key questions
For years, doctors worried about whether drugs to lower blood sugar would affect how people’s hearts function.
Now, results of a recent study show that DPP-4 inhibitors (a class of diabetes drugs) are safe for the heart. The results were presented at a meeting of the European Society of Cardiology and published in the New England Journal of Medicine.
The two specific DPP-4 drugs studied, alogliptin (Nesina) and saxagliptin (Onglyza), are antihyperglycemic, meaning they reduce glucose or sugar in the blood. They inhibit the function of dipeptidyl peptidase-4 (DPP-4), which is a protein that plays a role in blood sugar regulation.
Safety and testing
Diabetes drugs can have unexpected effects on the heart, so assuring the safety of DPP-4 drugs was a priority for Steven Nissen, MD, chairman of Cleveland Clinic’s Robert and Suzanne Tomsich Department of Cardiovascular Medicine and co-author of the EXAMINE study.
“We pushed very hard to get the Food and Drug Administration (FDA) to require outcome trials for diabetes drugs,” says Dr. Nissen. “We are getting a chance for the first time in 50 years to actually see what the outcomes are with drugs designed to lower blood sugar. That’s a huge step forward.”
The EXAMINE study followed 5,380 patients over a 40-month period. Participants in the study had type 2 diabetes and were recently hospitalized for acute myocardial infarction (heart attack) or unstable angina (pain in the heart caused by insufficient blood flow). Treating patients with the DPP-4 inhibitor alogliptin did not increase their risk for another cardiac event.
Another study, SAVOR TIMI 53, followed 16,492 patients with existing heart disease, or at high risk for heart disease. The study participants randomly received either a DPP-4 inhibitor (saxagliptin) or no medication (placebo) and were followed for two years.
In both studies, the effects of the DPP-4 inhibitors were “heart-neutral.” Dr. Nissen says that how you interpret the results depends partly on your point of view. “You can look at this as a glass half-empty or a glass half-full. Being neutral is certainly a good thing. We’ve worried over the years about blood sugar-lowering therapies that may increase adverse cardiovascular outcomes. These neither increased or decreased them,” he says.
No specific heart benefit
Though the DPP-4 inhibitors did not cause an increase in acute heart events, questions still remain about the impact of DPP-4 inhibitors on heart function, specifically heart failure. One of the studies, SAVOR TIMI 53, showed a possible increase in heart failure. That is why Dr. Nissen remains focused on continued scrutiny of diabetes drugs and heart function, noting that there was no indication that “aggressive glucose control…was protecting the heart.”
There is a delicate balance in managing diabetes and simultaneously protecting heart function. Although prudently cautious, Dr. Nissen sees the current DPP-4 studies as a glass half-full. “We haven’t found the magic bullet yet, but at least we now know that these drugs are safe and that’s a very good finding.”