In the largest trial of its kind to determine the cardiovascular outcomes for a new class of diabetes medications, Astra Zeneca’s Farxiga was found to significantly reduce the risk of heart failure and kidney problems in a broad group of patients with diabetes.
Farxiga is a new class drug, known as SGLT-2 inhibitors.
The effectiveness of SGLT-2 inhibitors among a broader population of patients, including those not previously diagnosed with heart disease, was not clear before the current trial.
The trial, however, did not show a statistically significant benefit in preventing heart-related problems in patients with existing cardiovascular disease.
Trial results were presented by Dr. Stephen Wiviott, a senior investigator in the TIMI Study Group and a cardiovascular medicine specialist at Brigham and Women’s Hospital, during the American Heart Association Scientific Sessions 2018.
“When it comes to helping our patients control and manage blood glucose, the ‘how’ appears to be as important than the ‘how much.’ When choosing a therapy, trial results like these can help us make an informed decision about what treatments are not only safe and effective for lowering blood glucose but can also reduce the risk of heart and kidney complications,” said Wiviott in a press release.
The results build upon two other recent trials of SGLT2 inhibitors that show this class of drugs improves heart and renal outcomes in patients with diabetes.
Farxiga is an SGLT-2 inhibitor that blocks glucose resorption in the kidneys and promotes the elimination of excess glucose through the urine.
Other SGLT-2 inhibitors have also shown favorable cardiovascular effects in patients with type 2 diabetes and established heart disease.
The effects of Farxiga was studied in patients with established heart disease as well as those with risk factors for heart disease.
The trial was a randomized, double-blind, multinational, placebo-controlled, phase 3b trial.
The study involved a total of 17,160 participants who were at least 40 years old and had type 2 diabetes.
It included 6,974 with established heart disease and 10,186 with risk factors for heart disease.
Participants received 10 mg of dapagliflozin daily or matched placebo.
The primary safety outcome was comprised of cardiovascular death, heart attack or stroke.
While the drug did not increase these events, it did not reduce the incidence in either patients with heart disease or with risk factors for heart disease.
However, the drug did lower blood glucose levels throughout the trial and the composite of cardiovascular death and hospitalization for heart failure was reduced by 17 percent, driven by a 27 percent reduction in hospitalization for heart failure.
The drug also improved renal outcomes, reducing a composite of several factors including end-stage renal disease and death due to renal failure.
Researchers saw no evidence of an increase in stroke, amputations or fracture, concerns raised from previous trials of this class of drugs.
As is known for this class of medications, there was an increase in genital infection and in diabetic ketoacidosis, but the latter was a rare event and the excess was less than 1 in 1,000 individuals per year.
The trial, Dapagliflozin Effect on CardiovascuLAR Events – Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) was sponsored by AstraZeneca, the drug’s manufacturer. Full disclosures available here.
The TIMI study group of Brigham and Women’s Hospital received a grant from AstraZeneca for the conduct of the DECLARE – TIMI 58 Trial.
Results have been published in the New England Journal of Medicine.
Diabetes drug prevents heart failure. EurekAlert! 2018, November 10. Retrieved: https://www.eurekalert.org/pub_releases/2018-11/bawh-ddp111018.php