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Randomized Controlled Trial
. 2020 Jun 4;18(1):165.
doi: 10.1186/s12916-020-01616-8.

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

João Pedro Ferreira  1   2 , Cyrus Mehta  3   4 , Abhinav Sharma  5 , Steven E Nissen  6 , Patrick Rossignol  7   8 , Faiez Zannad  7   8
Affiliations
Randomized Controlled Trial

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

João Pedro Ferreira et al. BMC Med. .

Abstract

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/1.73m2 and (2) eGFR < 60 ml/min/1.73m2. 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; interactionp = 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; interactionp = 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; interactionp = 0.013.

Conclusions: Alogliptin may benefit patients with eGFR ≥ 60, but may be detrimental to patients with eGFR < 60 ml/min/1.73m2. 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.

Keywords: Alogliptin; Outcomes; Renal function; Stratification.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Glycated hemoglobin levels over time by study treatment and renal function strata. p value < 0.001 for all time point comparisons within each eGFR stratum. Global p value for between eGFR strata interaction = 0.61. HgA1c, glycated hemoglobin; eGFR, estimated glomerular filtration rate
Fig. 2
Fig. 2
Cumulative incidence Kaplan-Meier curves by study treatment and renal function strata. p value for between eGFR strata interaction = 0.014. eGFR, estimated glomerular filtration rate
See this image and copyright information in PMC

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