Alogliptin in Patients with Type 2 Diabetes Receiving Metformin and Sulfonylurea Therapies in the EXAMINE Trial

BACKGROUND: We evaluated the antihyperglycemic efficacy and safety of adding the dipeptidyl dipeptidase-4 inhibitor alogliptin to metformin and sulphonylurea in the treatment of type 2 diabetes in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care Trial. METHODS: Patients with type 2 diabetes and recent acute coronary syndrome were randomized to alogliptin or placebo and standard of care. Participants were followed for up to 40 (median 18) months. In a subgroup taking metformin and sulphonylurea at baseline, we evaluated change from baseline in glycated hemoglobin (HbA1c), adverse events, cardiovascular outcomes, laboratory data, and other safety parameters. RESULTS: There were 1398 patients receiving baseline dual therapy (metformin and sulphonylurea only) randomized to alogliptin (N = 693) or placebo (N = 705); 550 patients receiving alogliptin and 505 patients receiving placebo completed the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care without addition of other antihyperglycemic therapies (P =.008). Changes from baseline to last visit in HbA1c were -0.4% on alogliptin and +0.1% on placebo (P <.001) in all those with baseline dual therapy and -0.4% for alogliptin and +0.2% for placebo (P <.001) in those without additional therapies. Reported rates of hypoglycemia were 8.8% for alogliptin and 6.7% for placebo (P =.16). Cardiovascular death and all-cause mortality rates were lower in those receiving alogliptin compared with those receiving placebo (hazard ratio, 0.49; 95% confidence interval, 0.28-0.84 and hazard ratio, 0.61; 95% confidence interval, 0.38-0.96, respectively). CONCLUSIONS: Addition of the dipeptidyl peptidase-4 inhibitor alogliptin to dual therapy with metformin plus sulfonylurea significantly reduced HbA1c and was well tolerated. Lower mortality rates were seen in patients treated with alogliptin in this subgroup. (C) 2018 Elsevier Inc. All rights reserved.