Endocrinologists Not Surprised by Cardiac Studies

Study results showing two DPP-4 inhibitors neither increased nor decreased the risk of cardiovascular events in type 2 diabetes patients came as no surprise to endocrinologists contacted by MedPage Today.

Both alogliptin (Nesina) and saxagliptin (Onglyza) had a null effect on risk of fatal and nonfatal cardiac events in the safety studies reported simultaneously at the European Society of Cardiology meeting here and online in the New England Journal of Medicine.

But neither did they diminish cardiovascular disease risk in patients with type 2 diabetes who'd either had a previous cardiovascular event or were at higher risk for heart disease, according to findings from the EXAMINE and SAVOR-TIMI 53 studies.

Endocrinologists contacted by MedPage Today said the results aren't unexpected, because the drugs haven't shown any signals of heart risk. And few were concerned by an increased risk of hospitalizations for heart failure that turned up in one of the trials.

"The neutral effects should not be surprising," Silvio Inzucchi, MD, director of the Yale Diabetes Center, told MedPage Today in an interview. "We've known that in DPP-4 inhibitors, cardiovascular parameters have been very modest."

On the other hand, Inzucchi said, the other drugs in the incretin class, GLP-1 agonists, "may potentially have greater cardiovascular effects. If those results would be neutral, then that might be considered disappointing. But DPP-4s have always been neutral on lipids and have shown no major effects on inflammatory markers."

Nesina (alogliptin) is a small-molecule, orally available dipeptidyl peptidase IV (DPP IV) inhibitor. DPP-4 inhibitors slow the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), both of which play a role in regulating blood glucose levels.

Nesina is specifically indicated as an adjunct to diet and exercise to improve glycemic control in adults with type II diabetes mellitus.

Nesina is supplied as a tablet for oral administration. The recommended dose is 25 mg once daily, with or without food.

Side Effects

Adverse events associated with the use of Nesina may include, but are not limited to, the following:

nasopharyngitis
headache
upper respiratory tract infection

Sue Kirkman, MD, an endocrinologist at the University of North Carolina Chapel Hill, called the results "reassuring."

"The point of the cardiovascular outcome studies is to make sure there are no off-target adverse effects on cardiovascular disease," Kirkman said in an email to MedPage Today. "It isn't to prove that the drugs reduce risk of cardiovascular disease. There are other reasons to treat hyperglycemia, such as symptom reduction and microvascular complication reduction."