December 21, 2018
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Liraglutide CV benefits consistent across kidney function, MI, stroke status

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New analyses from the LEADER study indicated that the CV benefits of liraglutide in patients with diabetes were consistent regardless of chronic kidney disease, prior MI or prior stroke.

As Cardiology Today previously reported, in the main results of the LEADER trial, liraglutide (Victoza, Novo Nordisk), a glucagon-like peptide-1 receptor agonist, was associated with lower risks for CV death, MI or stroke compared with placebo in 9,340 patients aged at least 50 years with poorly controlled type 2 diabetes.

In two analyses published in Circulation, researchers assessed whether the CV benefits of assignment to liraglutide in LEADER were consistent regardless of kidney function and whether they were consistent regardless of MI or stroke history.

Kidney function

For the kidney function analysis, Johannes F.E. Mann, MD, professor of medicine at KfH Kidney Center in Munich and the department of nephrology at Friedrich Alexander University of Erlangen, Germany, and colleagues stratified patients by estimated glomerular filtration rate (eGFR; < 60 mL/min/1.73 m2 or 60 mL/min/1.73 m2) and by whether they had albuminuria at baseline.

Mann and colleagues found the risk reduction associated with liraglutide for CV death/MI/stroke was greater in those with eGFR less than 60 mL/min/1.73 m2 (HR = 0.69; 95% CI, 0.57-0.85) than in those with eGFR of at least 60 mL/min/1.73 m2 (HR = 0.94; 95% CI, 0.83-1.07; P for interaction = .01).

The researchers did not find a consistent effect modification with liraglutide across more thoroughly stratified eGFR subgroups (P for interaction = .13) or when eGFR was analyzed as a continuous variable (P for interaction = .61).

The risk reduction associated with liraglutide for nonfatal stroke was significantly greater in patients with eGFR less than 60 mL/min/1.73 m2 (P for interaction = .004), whereas the risk reduction associated with nonfatal MI (P for interaction = .19) and CV death (P for interaction = .24) was numerically greater in those with impaired kidney function.

In addition, the risk reduction associated with liraglutide for CV death/MI/stroke was numerically but not significantly greater in those with baseline albuminuria vs. those without it (P for interaction = .36), Mann and colleagues wrote.

“The present results demonstrate that the results of the LEADER trial on CV efficacy and

on safety of liraglutide apply to patients with [chronic kidney disease], which is clinically important given

that those patients with type 2 diabetes and [chronic kidney disease] have a high CV risk burden and few

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options for antihyperglycemic therapies,” they wrote. “The benefits are evident in those with [chronic kidney disease] in addition to those without [chronic kidney disease].”

MI and stroke

For the MI/stroke analysis, Subodh Verma, MD, PhD, from the division of cardiac surgery at St. Michael’s Hospital and the University of Toronto, and colleagues stratified patients by whether they had prior MI or stroke (39.5%), established atherosclerotic CVD (ASCVD) without MI or stroke (33%) or risk factors alone (27.5%).

Liraglutide was associated with reducing CV death/MI/stroke in patients with prior MI/stroke (HR = 0.85; 95% CI, 0.73-0.99) and in patients with ASCVD but not MI/stroke (HR = 0.76; 95% CI, 0.62-0.94), but not in patients with risk factors only (HR = 1.08; 95% CI, 0.84-1.38; P for interaction = .11).

Similar trends were seen for the individual components of the primary outcome, according to the researchers.

“Liraglutide exerts a consistent benefit in patients with established atherosclerotic cardiovascular disease with and without a history of MI/stroke; however, it appears to be neutral in patients with cardiovascular risk factors alone,” Verma and colleagues wrote. “The reason for no apparent cardiovascular benefit in patients with cardiovascular risk factors alone could be that the baseline risk was lower, and to establish any potential effect might require a longer treatment period or larger sample size. Nevertheless, all patients with [type 2 diabetes] irrespective of risk group benefit from liraglutide treatment in regard to reduced renal outcomes, improved glycemic control, weight reductions, and better blood pressure control. These data may provide clinicians with important information to help identify appropriate patients who would most benefit from liraglutide therapy in their practice.” – by Erik Swain

Disclosures: The LEADER trial was funded by Novo Nordisk. Mann reports he received speaker honoraria from Amgen, Astra, Boehringer Ingelheim, Braun, Fresenius, Gambro, Eli Lilly, Medice, Novo Nordisk, Relypsa and Roche; research support from Boehringer Ingelheim, Celgene, Novo Nordisk, Roche and Sandoz; and consultant fees from AstraZeneca, Bayer, Celgene, Fresenius, Eli Lilly, Lanthio Pharma, Novo Nordisk, Relypsa, Sanifit and Vifor Pharma. Verma reports he research grants and/or speaker honoraria from Amgen, AstraZeneca, Boehringer Ingelheim/Eli Lilly, Janssen, Merck, Novartis, Novo Nordisk, Sanofi and Valeant. Please see the studies for the other authors’ relevant financial disclosures.