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

作者：White William B^*; Heller Simon R; Cannon Christopher P; Howitt Heena; Khunti Kamlesh; Bergenstal Richard M

来源：American Journal of Medicine, 2018, 131(7): 813-+.

DOI：10.1016/j.amjmed.2018.02.023

• Alogliptin
• Cardiovascular disease
• Diabetes
• Hypoglycemia
• Metformin
• Sulphonylurea

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.

• 出版日期2018-7