Alogliptin after acute coronary syndrome in patients with type 2 diabetes

White WB, Cannon CP, Heller SR, et al; for the EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369(14):1327-1335.

No increase in CV events with the DPP-4 inhibitor alogliptin was seen for the primary or secondary endpoints in the EXAMINE trial over median follow-up of 18 months.

Primary endpoint
The rate of the primary endpoint, a composite of CV death, nonfatal MI, or nonfatal stroke, by group:

  • Alogliptin (n=2,701): 11.3%
  • Placebo (n=2,679): 11.8%
  • Hazard ratio, 0.96 (95% CI, ≤1.16 [upper boundary of one-sided repeated CI]); P=0.32 for superiority; P<0.001 for noninferiority

Hazard ratios for the components of the primary endpoint were consistent with the hazard ratio for the composite endpoint (data not shown).

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EXAMINE: No Increase in CV Events with Alogliptin Primary Endpoint
 

Secondary endpoint
The rate of the secondary endpoint, the primary endpoint plus urgent revascularization due to unstable angina within 24 hours after hospital admission, by group:

  • Alogliptin (n=2,701): 12.7%
  • Placebo (n=2,679): 13.4%
  • Hazard ratio, 0.95 (95% CI, ≤1.14 [upper boundary of one-sided repeated CI]); P=0.26 for superiority

Hazard ratios for the additional endpoints of death from any cause and death from CV causes were consistent with the hazard ratio for the primary composite endpoint: 0.88 (95% CI, 0.71-1.09) and 0.85 (0.66-1.10), respectively (data not shown).

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EXAMINE: No Increase in CV Events with Alogliptin Secondary Endpoint
 

A1C change from baseline
Significantly greater change in A1C from baseline was seen in with alogliptin versus placebo. Mean change in A1C:

  • Alogliptin (n=2,701): -0.33%
  • Placebo (n=2,679): 0.03%
  • Least squares mean between-group difference: -0.36 percentage points (95% CI, -0.43 to -0.28; P<0.001)

Baseline A1C was 8.0% in both groups.

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EXAMINE: Significantly Greater A1C Change from Baseline with Alogliptin Vs Placebo 

Adverse events
There was no significant between-group difference in the occurrence of serious adverse events in the EXAMINE study: alogliptin 33.6%, placebo 35.5% (P=0.14). Similar rates of the following were seen in the alogliptin and placebo groups:

  • Hypoglycemia
  • Acute and chronic pancreatitis (no fatal cases)
  • Changes in eGFR and dialysis initiation

There was no significant between-group difference in cancer incidence and there were no reports of pancreatic cancer.

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EXAMINE: Adverse Events
 

About EXAMINE
EXAMINE was a randomized, double-blind, noninferiority trial investigating the CV safety of the DPP-4 inhibitor alogliptin in subjects with type 2 diabetes and ACS. Participants (N=5,380) were receiving antihyperglycemic therapy (other than a DPP-4 inhibitor or GLP-1 receptor agonist), had ACS 15-90 days prior to randomization, and had A1C 6.5% to 11% (7% to 11% if taking insulin). ACS included acute MI and UA requiring hospitalization.

Subjects were randomized to daily alogliptin (based on eGFR) or placebo. The alogliptin dose was 25 mg daily for eGFR ≥60 mL/min/1.73 m2; 12.5 mg daily for eGFR 30 to <60 mL/min/1.73 m2; 6.25 mg daily for eGFR <30 mL/min/1.73 m2. The majority of subjects (71.4%) received the 25-mg alogliptin dose. Subjects received background diabetes and CVD medications.

The primary endpoint was a composite of CV death, nonfatal MI, or nonfatal stroke. The secondary endpoint was the primary composite endpoint plus urgent revascularization due to UA within 24 hours of hospital admission. Median follow-up was 18 months.

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EXAMINE: Design
 

Alogliptin is not FDA approved for cardiovascular risk reduction.

EXAMINE=Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care
ACS=acute coronary syndrome; CV=cardiovascular; CVD=cardiovascular disease; DPP-4 inhibitor=dipeptidyl peptidase-4 inhibitor; eGFR=estimated glomerular filtration rate; GLP-1 receptor agonist=glucagon-like peptide-1 receptor agonist; MI=myocardial infarction; UA=unstable angina  

  

The pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual prescribing information for approved uses outside of the United States. 

October 2013

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

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Last Modified: 3/23/2015