Based on a study mandated by FDA to study for possible adverse drug event signals post-marketing, Onglyza (saxagliptin) has been shown to produce a 0.7% absolute risk (27% relative risk) for heart failure exacerbation in heart failure patients. The SAVOR-TIMI 53 trial was designed to test the cardiovascular safety of saxagliptin. NEJM 2013;369:1317-1326. The largest number of hospitalizations occurred in those with BNP levels greater than 333 pg/ml, suggesting BNP as a risk factor. Also, hospitalizations tended to occur most frequently in the first six months of therapy.
It should be noted that there are no data to say that saxgliptin should NOT be used in those with heart failure, but each case should be reviewed individually to assess benefits versus risks of continued therapy. From guidelines for the management of diabetes in older adults, if average blood glucose is below an A1C of 7%, then perhaps consideration for review of saxagliptin therapy is warranted, since A1C lowering below most older adults ( >75 years old) may not be associated with better outcomes but actually poorer outcomes.
Questions that arise from this data are:
- Does this play significantly into the role of re-hospitalization rates for CHF?
- Is this a class effect of DPP-4 inhibitors?