Liraglutide Cuts Risk of Cardiovascular Deaths

With commentary by John Buse, MD, PhD, chief of endocrinology, University of North Carolina School of Medicine, Chapel Hill.

Liraglutide (Victoza), a drug used to help control blood sugar levels in type 2 diabetes, also reduces the risk of dying from heart disease, new research suggests. Those taking the drug, compared to those taking placebo, had a 22% lower risk of cardiovascular-related death during the follow-up period.


"You are taking liraglutide to improve blood sugar control, but as a benefit, there seems to be this reduction in cardiovascular events," says John Buse, MD, PhD, chief of endocrinology at the University of North Carolina School of Medicine, Chapel Hill. He is the senior author of the study, presented at the American Diabetes Association annual meeting in New Orleans this week and published simultaneously in the New England Journal of Medicine.

Determining which drugs taken to control diabetes may protect the cardiovascular system is especially crucial. Those with type 2 diabetes are twice as likely to have a heart attack or a stroke, according to the American Diabetes Association. 

Study Details

For the new study, researchers followed more than 9,000 patients with type 2 diabetes for about four years. They randomly assigned half to take liraglutide, which was added on to whatever other medicines they took for their diabetes, and the other half to take placebo in addition to their other medicines.

The aim of the study was to see if those on liraglutide had a lower risk of three different outcomes: dying of cardiovascular disease or having nonfatal heart attack or nonfatal stroke. When they separated out the three outcomes—cardiovascular death, nonfatal heart attack or nonfatal stroke—they found that fewer patients on the liraglutide died during the four-year follow-up period from cardiovascular causes than those not on it. While 4.7% (219) of those in the liraglutide group died of cardiovascular causes, 6% (278) of those not on it died. Those in the liraglutide group were also less likely to die during the follow up period of any cause.

Those on liraglutide were also less likely than those on placebo to have a nonfatal heart attack or stroke, but the differences between groups were not significant from a statistics point of view.

The study is known as the LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results). It was funded by Novo Nordisk, Victoza's maker, and the National Institutes of Health.

Bottom line? "Liraglutide or Victoza seems safe and is effective to reduce important outcomes for people with diabetes,'' Dr. Buse says.

Dr. Buse cannot explain why the drug helps. It is known, he says, that drugs such as liraglutide have a broad-based effect on the vascular system. "It seems to be an effect on the general process of hardening of the arteries," Dr. Buse says.

About Liraglutide

Approved by the FDA in 2010, liraglutide is not meant to be used as ''first-line'' therapy. Instead, it is added on when diet, exercise and other medicines don't keep the diabetes under control well enough. Liraglutide is an injection, available in doses of .6, 1.2 and 1.8 milligrams, 

The same ingredient, liraglutide, is in the drug Saxenda, approved for weight loss. But Saxenda's dose is higher, 3 mg.

Liraglutide is known as a glucagon-like peptide 1 (GLP1) analogue. It works by helping the pancreas release the right amount of insulin when blood sugar levels are high, so the insulin can move the sugar from the blood into other body tissues for energy. 

Among precautions with its use are its possible association with inflammation of the pancreas, or pancreatitis. In animals, a rare thyroid cancer was linked with its use, the FDA says.

Perspectives on LEADER study

The study findings are reassuring about the drug's cardiovascular safety, says Shari Bolen, MD, MPH, assistant professor of medicine, MetroHealth/Case Western Reserve University, who reviewed the findings and has researched diabetes drugs. 

However, she had some caveats, citing the need for longer-term studies of these drugs to truly determine differences. "You need long-term studies to determine differences since these cardiovascular outcomes such as heart attacks are generally rare events," Dr. Bolen says. "You need enough rare events to determine if there are differences between groups."

Even so, she says, the good news from this study is that ''this drug does not appear to worsen cardiovascular risk," found to be a problem with some other drugs.

Despite the reassuring finding, she says, some patients have issues with drugs that need to be injected, so may not be eager to use liraglutide.

Questions about the best combination of treatments for type 2 diabetes are still being sorted out, she says. The GRADE study, or Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study, is underway now. "Results of the GRADE study should help with this decision in the future," Dr. Bolan says. 

The findings of the new study are important, says Gerald Bernstein, MD, program coordinator of the Friedman Diabetes Program at Lenox Hill Hospital, New York, and a former president of the American Diabetes Association. The results may put some worry to rest. "In recent years, the concern about cardiovascular risk and negative outcomes have put pressure on new drugs and their studies," he says. The study is helpful, he says, especially as drugs of this type increase in use. He agrees that how the drugs work has yet to be fully explained, ''other than glucose control."

In a 2015 study, researchers reported that another glucose-lowering drug, empagliflozin (Jardiance), approved in 2014 as a solo or add-on treatment, was found to reduce risk of cardiovascular death by 38%. 

Dr. Buse reports receiving fees and holding stock options in PhaseBio, involved in developing drugs for diabetes and other conditions.


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