Clear data about whether diabetes drugs that lower sugar levels may also reduce the risk of heart attack are not available and some evidence suggests diabetes drugs may actually raise the risks. Now, in new findings from a large, international clinical trial led by researchers at Brigham and Women’s Hospital (BWH), researchers find no excess in the risk of heart attacks with the use of saxagliptin, a new diabetes drug. However, researchers note that there was no reduction in heart attack risk, and an unexpected increase in hospitalization for heart failure in patients who received the drug was seen. These results were presented at the European Society Cardiology 2013 Congress in Amsterdam and published simultaneously in the New England Journal of Medicine.
Deepak L. Bhatt, MD, MP
“We hope these findings will help to guide physicians and improve their ability to prescribe different diabetes drugs in a more evidence-based and data-driven way,” said study co-principal investigator Deepak L. Bhatt, MD, MPH, from the VA Boston Healthcare System and the TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School. “Few diabetes drugs have been studied as thoroughly as saxagliptin, and this outcome trial raises the bar for evaluating the safety of all diabetes drugs.”
The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR-TIMI 53) trial was designed to determine the effect of the diabetes drug saxagliptin (Onglyza), a selective dipeptidyl peptidase 4 (DPP-4) inhibitor, on heart attack risk. This large, double-blind, placebo-controlled international study was conducted at 788 sites in 26 countries and included 16,492 patients with type 2 diabetes mellitus (with HbA1c levels between 6.5 and 12 percent and either established or multiple risk factors for cardiovascular disease) who were randomized to receive either saxagliptin 5 mg daily (or 2.5 mg daily in patients with renal impairment) or matching placebo over a median of 2.1 years of follow up. Treatment with all other diabetes and cardiovascular medications was left to the discretion of the treating physician.
Researchers found no excess in the risk of heart attacks with the use of saxagliptin, which was the primary safety goal of the study. Specifically, the primary endpoint, which was a composite of cardiovascular death, non-fatal heart attack, or non-fatal ischemic stroke was similar in intervention and control groups (7.3% in saxagliptin group compared to 7.2% in the placebo group).
Researchers also report that the secondary endpoint of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 12.8 percent of patients who received saxagliptin group compared to 12.4 percent who were in the placebo group.
“We are reassured by the lack of any increase in the risk for heart attack among patients receiving this drug,” said Benjamin Scirica, MD, MPH, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School.
“Patients who received saxagliptin also had better control of blood sugar levels and a reduced need for insulin therapy. Saxagliptin also prevented progression of microalbuminuria,” said co-principal investigator Itamar Raz, MD, Hadassah Medical Center, Israel.
Related to blood sugar levels, researchers report that patients treated with saxagliptin were more likely to achieve a glycated hemoglobin level less than 7 percent at the end of treatment. However, an increased number of patients also reported at least one hypoglycemic event in the treatment group when compared with placebo (15.3 vs. 13.4 percent).
“Our data also show an increase in hospitalization for heart failure in patients who received saxagliptin, which was not expected and deserves further study,” said study chairman Eugene Braunwald, MD, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School.
This research was supported Funded by AstraZeneca/Bristol-Myers Squibb; SAVOR-TIMI 53 ClinicalTrials.gov number, NCT01107886.
The TIMI study group and Hadassah Medical Center received research support from AstraZeneca and Bristol-Myers Squibb.
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