CV Safety of Diabetes Drugs on ADA 2015 Program

Hi. I am Dr Anne Peters, and today I want to provide updates on cardiovascular outcomes trials of three DPP-4 inhibitors and one GLP-1 receptor agonist.

The basic news is that none of these trials found a worsening or an improvement in cardiovascular outcomes. The drugs were similar to placebo in terms of the primary outcomes. The one deviation is the SAVOR-TIMI trial of saxagliptin, which showed an increase in rates of congestive heart failure requiring hospitalization.

Drilling Down Into the Details

The two trials that have the longest follow-up are the EXAMINE^[1] and SAVOR-TIMI^[2] trials. EXAMINE enrolled approximately 5500 individuals who had recently suffered acute coronary syndrome. They were very sick individuals. They received either alogliptin or placebo, and the study found no difference in terms of the cardiovascular outcomes. The SAVOR-TIMI trial compared saxagliptin and placebo in approximately 16,500 individuals who were at high risk for cardiovascular events but who had not experienced any recent cardiovascular events. As mentioned, SAVOR-TIMI showed no difference in rates of cardiovascular endpoints, but it did find an increased risk for congestive heart failure requiring hospitalization.

The US Food and Drug Administration was concerned enough about these findings that they held a special hearing on April 14, 2015, to discuss these trials and decide whether the findings warrant a change in labeling of these drugs.