EXAMINE Finds No Increased Risk of CV Events with Alogliptin for Diabetes Patients

"They did not show increased cardiac risk – a rather neutral trial in terms of the drug, which was lowering the hemoglobin A1c, but did not adversely impact CV risk," said Spencer King, MD, MACC.
Treatment with the dipeptidyl peptidase (DPP)-4 inhibitor alogliptin in patients with type 2 diabetes and high cardiovascular risk due to recent acute coronary syndromes did not increase cardiovascular morbidity and mortality compared with placebo, according to findings presented Sept. 2 at the ESC Congress 2013 in Amsterdam and simultaneously published in the New England Journal of Medicine.

The double-blind, non-inferiority Examination of Cardiovascular Outcomes with Alogliptin Versus Standard of Care (EXAMINE) trial randomized 5,380 patients from 49 countries to receive alogliptin or placebo along with standard-of-care treatment for type 2 diabetes and cardiovascular risk factors. The drug was given in daily doses of 25 mg, 12.5 mg or 6.25 mg, depending on each patient's kidney function.

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After a median follow-up period of 18 months, the primary endpoint of the study — a composite of cardiovascular death, nonfatal MI, and nonfatal stroke — occurred at similar rates in the two groups of patients: 11.3 percent in the alogliptin-treated group versus 11.8 percent in the placebo group (P for non-inferiority < 0.001). In addition, hemoglobin A1c levels were significantly lower in the alogliptin-treated patients, with a mean decrease from baseline of 36 percent.

Outcomes also were similar in both groups for the secondary endpoint: a composite of cardiovascular death, nonfatal MI, nonfatal stroke and urgent revascularization due to unstable angina. The incidence of hypoglycemia, pancreatitis, malignancy and dialysis was similar in both groups as well.

"The findings could guide clinicians to choose among the many anti-diabetic agents available when treating patients with type 2 diabetes and very high cardiovascular risk," said William B. White, MD, chair of EXAMINE's steering committee and professor of medicine at the University of Connecticut School of Medicine, Farmington.

"However, EXAMINE does not rule out longer-term benefits or risks of alogliptin with respect to cardiovascular endpoints, as the median duration of the trial was approximately 18 months," he adds.

The study was undertaken to satisfy U.S. Food and Drug Administration requirements that new diabetes drugs undergo clinical trials to rule out cardiovascular risks.

Keywords: Stroke, Uracil, Acute Coronary Syndrome, Follow-Up Studies, Pancreatitis, Diabetes Mellitus, Type 2, Risk Factors, Hypoglycemia, Glycated Hemoglobin A, Renal Dialysis, Incidence, Piperidines, United States Food and Drug Administration, Cardiovascular Diseases, Hypoglycemic Agents

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