medwireNews: Findings of the LEADER trial show that liraglutide treatment may confer a reduced risk of cardiovascular events in patients with Type 2 diabetes and a high vascular risk.
The LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial was designed specifically to assess the cardiovascular safety profile of the glucagon-like peptide (GLP)-1 receptor agonist liraglutide when taken by this subgroup of diabetes patients.
The investigators – John Buse (University of North Carolina School of Medicine, Chapel Hill, USA) and colleagues – hypothesised that liraglutide would be noninferior to placebo for the primary outcome of nonfatal myocardial infarction or stroke, or cardiovascular death.
In fact, liraglutide was statistically superior, with 13.0% of the liraglutide group and 14.9% of the placebo group having a primary outcome event over a median 3.8 years of follow-up, equating to a significant 13% risk reduction. The benefit was consistent across subgroups including age, race, diabetes duration and starting glycated haemoglobin level.
This would equate to needing to treat 66 patients with liraglutide to prevent one primary outcome event over 3 years, the team reports in The New England Journal of Medicine.
The 4668 patients randomly assigned to receive subcutaneous liraglutide took it at a dose of 1.8 mg per day. This group also had significantly improved microvascular outcomes compared with the 4672 patients taking placebo, with retinopathy or nephropathy event rates of 7.6% versus 8.9%.
LEADER patients were aged at least 50 years with co-existing cardiovascular disease or at least 60 years with one or more cardiovascular risk factors. All patients had a baseline glycated haemoglobin level of at least 7.0%, with the average being 8.7%.
Rates of adverse events and serious adverse events did not differ significantly by treatment. Rates of adverse events leading to discontinuation were significantly higher in the liraglutide than placebo group, at 9.5% versus 7.3%, because of higher rates of gastrointestinal events.
The team note previous concerns about heart failure risk in patients taking diabetes medications, but this was not borne out in the current study, with hospitalisation for heart failure occurring no more often in the liraglutide group than the placebo group, at 4.7% and 5.3%, respectively.
However, Buse et al also observe that previous trials of antidiabetic medications, including the GLP-1 receptor agonist lixisenatide, did not demonstrate cardioprotective benefits.
They note that the LEADER trial had greater statistical power than most previous studies, and recruited patients whose blood glucose was poorly controlled at baseline. But otherwise, they say there is “no obvious single explanation” for the conflicting study findings.
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