Alogliptin after acute coronary syndrome in patients with type 2 diabetes: a renal function stratified analysis of the EXAMINE trial.

BACKGROUND

The EXAMINE trial tested the efficacy and safety of alogliptin, an inhibitor of dipeptidyl peptidase 4, compared with placebo in 5380 patients with type 2 diabetes and a recent acute coronary syndrome. Because alogliptin is cleared by the kidney, patients were stratified according to screening renal function within two independently randomized strata: (1) estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73m and (2) eGFR < 60 ml/min/1.73m. We aim to assess the efficacy and safety of alogliptin vs. placebo according to the renal function strata.

METHODS

Cox-proportional hazard models with an interaction term by renal function strata were used. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke.

RESULTS

Patient characteristics were balanced within each renal function strata. In total, 3946 patients were randomized within the eGFR ≥ 60 stratum, and 1434 patients within the eGFR < 60 stratum. The effect of alogliptin was modified by the renal function strata.

PRIMARY OUTCOME

eGFR ≥ 60 HR = 0.81, 95%CI, 0.65-0.99, and eGFR < 60 HR = 1.20, 95%CI, 0.95-1.53; interaction = 0.014. Cardiovascular death: eGFR ≥ 60 HR = 0.61, 95%CI, 0.42-0.88, and eGFR < 60 HR = 1.16, 95%CI, 0.82-1.65; interaction = 0.013. Non-fatal MI: eGFR ≥ 60 HR = 0.86, 95%CI, 0.66-1.13, and eGFR < 60 HR = 1.48, 95%CI, 1.07-2.06; interaction = 0.013.

CONCLUSIONS

Alogliptin may benefit patients with eGFR ≥ 60, but may be detrimental to patients with eGFR < 60 ml/min/1.73m. These hypothesis-generating findings require further validation to assess the potential benefit and risk of alogliptin across the renal function spectrum among patients with type 2 diabetes and a recent acute coronary syndrome.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT00968708.