A US Food and Drug Administration (FDA) independent advisory committee voted in April that a cardiovascular safety signal for two antidiabetes dipeptidyl peptidase 4 (DPP4) inhibitors — AstraZeneca's saxagliptin and Takeda's alogliptin — could be handled by updating the drugs' labels.

The panel was convened to discuss the results of two post-approval cardiovascular outcome studies. In the 16,492-patient SAVOR trial, saxagliptin was associated with a 27% increase in risk of hospitalization for heart failure (New Engl. J. Med. 369, 1317–1326; 2013). In the 5,380-patient EXAMINE trial, alogliptin was associated with a numerical increase in hospitalization for heart failure, but the effect was not as marked as with saxagliptin (New Engl. J. Med 369, 1327–1335; 2013). An FDA sensitivity analysis of the saxagliptin data also suggested “significant or near-significant increases in all-cause mortality,” according to a regulatory briefing released before the meeting.

Panellists were concerned by the increased risk of hospitalization for heart failure in particular, but voted 13 to 1 that saxagliptin had an acceptable cardiovascular risk profile (with 1 abstention). 14 panellists voted to update the labelling and 1 voted to withdraw the drug from the market. The voting was more favourable for alogliptin, with 13 experts voting to update the label and 3 voting that no changes were needed.

The FDA often follows the recommendations of its panellists, but it doesn't have to.

The jury is still out, however, on whether the adverse cardiovascular effects are class effects. Merck & Co. will present cardiovascular outcome data from a post-marketing study of its market-leading sitagliptin at the American Diabetes Association meeting in June. If there is a class effect that has an impact on sales, Merck is likely to take the biggest hit. Merck earned around US$4 billion from sitagliptin in 2014. In the same year, AstraZeneca earned over $800 million from saxagliptin, and Takeda earned over $400 million from alogliptin.