Alogliptin after acute coronary syndrome in patients with type 2 diabetes

EXAMINE Investigators

Research output: Contribution to journalArticle

1556 Citations (Scopus)

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 (US)
Pages (from-to)1327-1335
Number of pages9
JournalNew England Journal of Medicine
Volume369
Issue number14
DOIs
StatePublished - Jan 1 2013

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Acute Coronary Syndrome
Type 2 Diabetes Mellitus
Placebos
Hypoglycemic Agents
Dipeptidyl-Peptidase IV Inhibitors
Myocardial Infarction
Cardiovascular Agents
Unstable Angina
Glycosylated Hemoglobin A
Random Allocation
alogliptin
Hypoglycemia
Pancreatitis
Dialysis
Cause of Death
Hospitalization
Stroke
Confidence Intervals
Safety
Drug Therapy

ASJC Scopus subject areas

  • Medicine(all)

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Alogliptin after acute coronary syndrome in patients with type 2 diabetes. / EXAMINE Investigators.

In: New England Journal of Medicine, Vol. 369, No. 14, 01.01.2013, p. 1327-1335.

Research output: Contribution to journalArticle

EXAMINE Investigators. / Alogliptin after acute coronary syndrome in patients with type 2 diabetes. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 14. pp. 1327-1335.
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T1 - Alogliptin after acute coronary syndrome in patients with type 2 diabetes

AU - EXAMINE Investigators

AU - White, William B.

AU - Cannon, Christopher P.

AU - Heller, Simon R.

AU - Nissen, Steven E.

AU - Bergenstal, Richard M.

AU - Bakris, George L.

AU - Perez, Alfonso T.

AU - Fleck, Penny R.

AU - Mehta, Cyrus R.

AU - Kupfer, Stuart

AU - Wilson, Craig

AU - Cushman, William C.

AU - Zannad, Faiez

AU - Aiub, J.

AU - Albisu, J.

AU - Alvarez, C.

AU - Astesiano, A.

AU - Barcudi, R.

AU - Bendersky, M.

AU - Bono, J.

AU - Bustos, B.

AU - Cartasegna, L.

AU - Caruso, O.

AU - Casabe, H.

AU - Castro, R.

AU - Colombo, H.

AU - Cuneo, C.

AU - Cura, F.

AU - De Loredo, L.

AU - Dran, R.

AU - Fernandez, H.

AU - Garcia Pinna, J.

AU - Hrabar, A.

AU - Klyver de Saleme, M.

AU - Luquez, H.

AU - Mackinnon, I.

AU - Maffei, L.

AU - Majul, C.

AU - Mallagray, M.

AU - Marino, J.

AU - Martinez, D.

AU - Martingano, R.

AU - Nul, D.

AU - Parody, M. L.

AU - Petrucci, J.

AU - Pieroni, M.

AU - Piskorz, D.

AU - Prado, A.

AU - Ramos, H.

AU - Resk, J.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

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