Alogliptin after acute coronary syndrome in patients with type 2 diabetes

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Abstract

BACKGROUND: To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome. METHODS: We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo. CONCLUSIONS: Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo.

Original languageEnglish
Pages (from-to)1327-1335
Number of pages9
JournalNew England Journal of Medicine
Volume369
Issue number14
DOIs
StatePublished - 2013

Bibliographical note

Funding Information:
This research was partially supported by The Grant-in-Aid for Scientific Research (B) (#26287020) Japan Society for the Promotion of Science. The author would like to thank Professor Shigeru Sakaguchi (Tohoku University), who is his supervisor, for suggesting this interesting problem and for many stimulating discussions. Also the author would like to thank Lorenzo Cavallina (Tohoku University) for warm encouragement and constructive comments. Moreover the author is grateful to the referees for their constructive suggestions.

Funding Information:
AMS Subject Classifications: 35J20, 35P20. Accepted for publication: January 2018. This research was partially supported by the Grant-in-Aid for Scientific Research (B) (#26287020) Japan Society for the Promotion of Science.

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