Diabetes drugs lower risk of cardiovascular death and kidney disease

John Murphy, MDLinx | June 14, 2016

People with diabetes are at high risk for cardiovascular and renal diseases. New studies report that the drug empagliflozin significantly reduced the risk of kidney disease and another drug, liraglutide, lowered the risk of cardiovascular disease and death in diabetes patients.

Advertisement

Diabetes drugs linked to reduced cardiovascular & kidney disease

New studies report on diabetes drugs that reduce the risk of kidney disease and lower the risk of cardiovascular disease and death in patients with diabetes.

These results were presented at the American Diabetes Association 76th Scientific Sessions, held June 10-14, 2016 in New Orleans, LA, and simultaneously published in the New England Journal of Medicine.

LEADER Trial

The first study—the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial—involved 9,340 adults with type 2 diabetes who were at high risk of heart disease, and took place at 410 sites in 32 countries. Half of the participants were given a daily liraglutide injection, and half were given a placebo injection, along with standard care.

The trial lasted three years. Compared with patients on placebo, those in the liraglutide group showed:

  • 13% lower overall risk of a heart attack or stroke, or of dying from cardiovascular cause

  • 15% lower risk of all-cause mortality

  • 22% lower risk of cardiovascular mortality

  • 22% lower risk of new evidence of advanced kidney disease

“This is the first diabetes drug that has shown across-the-board benefits for cardiovascular diseases, and this suggests it plays a role in treating atherosclerosis, which is what leads to heart attacks and strokes,” said the study’s senior author John Buse, MD, PhD, Director of the University of North Carolina (UNC) Diabetes Care Center, in Chapel Hill, NC.

“This changes the whole conversation about treating diabetes,” added Dr. Buse, who is also the Verne S. Caviness Distinguished Professor of Medicine at the UNC School of Medicine. “To date, people have taken diabetes drugs to lower blood sugar. Now we can say that they should take liraglutide to prevent or delay the worst things that occur commonly in diabetes—heart attacks, strokes, advanced kidney disease, and death.”

EMPA-REG OUTCOME Trial

The other study—Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME)—included 7,020 patients at 590 sites in 42 countries. These patients had type 2 diabetes, established cardiovascular disease, and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body surface area.

Researchers randomly assigned the patients to receive either empagliflozin (at a 10 mg or 25 mg dose) or placebo once daily, in addition to standard care.

During the three-year trial, empagliflozin reduced the risk for new-onset or worsening kidney disease by 39%, compared with placebo. Other results of empagliflozin treatment, when compared with placebo, included:

  • 55% lower risk for starting renal replacement therapy

  • 44% lower risk for doubling of serum creatinine level

  • 38% lower risk for progression to macroalbuminuria

“These findings are clinically important, given that more than a third of people with type 2 diabetes will develop kidney disease, which can lead to kidney failure and eventually the need for dialysis,” said study author Christoph Wanner, MD, Chief of the Division of Nephrology and Hypertension at Würzburg University Hospital, in Würzburg, Germany.

“Since diabetes is the number one cause of kidney failure in the US, novel treatments that may have the potential to help address this crucial medical need are necessary,” Dr. Wanner added.

EMPA-REG OUTCOME had previously shown that empagliflozin also reduced the risk of cardiovascular death by 38% with no significant difference in the risk of non-fatal heart attack or non-fatal stroke.

Not a ‘Home Run’

In an accompanying editorial in the New England Journal of Medicine, Julie R. Ingelfinger, MD, and Clifford J. Rosen, MD, noted that diabetes drugs in other trials have not shown similar results. They questioned whether the difference in results between these drugs and others might be due to inclusion and exclusion criteria in the specific trials.

However, “although there may have been differences among the participants that account for the positive results in the EMPA-REG OUTCOME and LEADER trials, such differences alone do not fully explain the results. We are left with differences that appear encouraging, yet are not a ‘home run’ with regard to the management of diabetes,” they wrote.

“In the coming years, controlled and comparative effectiveness trials that uniformly combine newer agents with older agents may help to delineate an even more effective treatment plan for the millions of people whose lives are affected by type 2 diabetes,” they concluded.

The LEADER trial was funded by Novo Nordisk and the National Institutes of Health. The EMPA-REG OUTCOME trial was funded by Boehringer Ingelheim, Eli Lilly, and Company Diabetes Alliance.

Advertisement