Allan S. Brett, M

In fairly short studies, saxagliptin and alogliptin neither decreased nor increased the incidence of major adverse CV events.

In two industry-sponsored, randomized, international trials, investigators examined the effect of dipeptidyl peptidase–4 (DPP-4) inhibitors on the primary endpoint of cardiovascular-related death, myocardial infarction, or stroke in patients with type 2 diabetes. The studies were conducted in response to the FDA's requirement that cardiovascular safety be demonstrated for new diabetes drugs.

In one trial, 16,500 patients (mean age, 65; median duration of diabetes, 10 years) with additional cardiovascular risk factors or known cardiovascular disease received saxagliptin (Onglyza) or placebo. During average follow-up of 2 years, the primary endpoint occurred with near-identical frequency in the two groups (7.3% and 7.2%). No differences in secondary cardiovascular endpoints were noted, except for slightly higher incidence of heart failure hospitalizations with saxagliptin (3.5% vs. 2.8%; P=0.007). Mean glycosylated hemoglobin (HbA1c) was 0.2% lower in the saxagliptin group than in the placebo group, and hypoglycemia was more common with saxagliptin (15.3% vs. 13.4%; P<0.001).

In the other trial, 5400 diabetic patients who had suffered acute coronary syndrome during the previous 3 months received either alogliptin (Nesina) or placebo. During median follow-up of 1.5 years, the incidence of the primary endpoint was 11.3% with alogliptin and 11.8% with placebo, indicating noninferiority (but not superiority) of alogliptin. Alogliptin lowered HbA1c by 0.3% compared with placebo but did not increase risk for hypoglycemia.

Citation(s):

Scirica BM et al. for the SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013 Sep 2.

White WB et al. for the EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013 Sep 2.