Liraglutide performs well in diabetic kidney disease

By Gene Emery

NEW YORK (Reuters Health) - Fourteen months after the LEADER study showed that the injectable diabetes drug liraglutide lowered the risk of heart attack, stroke and cardiovascular death by 13%, a further analysis reveals that the treatment also reduces the odds of renal problems by 22% compared to placebo.

The rate of a composite index of death due to renal disease, end-stage renal disease, new-onset persistent macroalbuminuria, or persistent doubling of serum creatinine was 7.2% with placebo versus 5.7% with the drug, sold by Novo Nordisk under the brand name Victoza (P=0.003).

"The two bad outcomes in diabetes we don't really have good control of are cardiovascular disease and kidney disease," coauthor Dr. John Buse told Reuters Health by telephone. "With the combination of both endpoints being reduced, I think it's a meaningful difference for patients with diabetes" and worth the cost.

The drug costs about $6,800 per year at the lower 1.2-mg daily dose, $10,100 annually at the higher 1.8-mg dose. Its price is one reason doctors typically prescribe it as a third or fourth option after patients try various oral medicines.

Novo Nordisk helped to fund the study.

About 1 in 4 U.S. adults with diabetes suffer from diabetic kidney disease.

In the new study, published online August 30 in the New England Journal of Medicine, median follow-up was 3.8 years. All 9,340 patients were considered to have high cardiovascular risk and received usual care.

The biggest difference in outcome was new-onset persistent macroalbuminuria: in 3.4% of drug recipients versus 4.6% of placebo recipients (P=0.004).

The two groups did not differ significantly in their odds of end-stage renal disease and a persistent doubling of serum creatinine levels.

Estimated glomerular filtration rates declined continuously in both groups, but slightly slower with liraglutide.

"The mechanism behind the effect of liraglutide on the renal outcomes is unclear," said the research team, led by Dr. Johannes Mann of the KfH Kidney Center in Munich, Germany.

Dr. Buse, a professor of medicine at the University of North Carolina School of Medicine, said that because the evidence now shows that liraglutide, a glucagon-like peptide 1 (GLP-1) annalogue, as well as sodium-glucose-cotransporter 2 (SGLT2) inhibitors, can help mitigate cardiovascular and kidney damage, they should be used more broadly despite their expense.

He said fewer than 10% of patients with diabetes get liraglutide, and that an even smaller percentage get an SGLT2 inhibitor, which he called "a serious problem for the translation of these important research findings into common clinical practice. It's almost a scandal."

In an accompanying editorial, Dr. Ian de Boer of the University of Washington in Seattle said, "Currently, it is logical to consider including a GLP-1 agonist or SGLT2 inhibitor in the glucose-lowering regimen of patients with type 2 diabetes and mild-to-moderate diabetic kidney disease, with the anticipation of salutary renal and, particularly, cardiovascular effects."

The most common side effects of liraglutide are nausea, vomiting and other gastrointestinal symptoms, which appear at least once in about a third of patients over several years.

"In general, it tends to get better over time, so if people can tough it out for a while, they can work through it," said Dr. Buse.

The LEADER trial identified no increased risk of pancreatitis with liraglutide, which had been a concern.

Victoza had sales of $2.7 billion last year.

SOURCE: http://bit.ly/2vBCVYY

N Engl J Med 2017.

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