medwireNews: The glucagon-like peptide (GLP)-1 receptor agonist dulaglutide has demonstrated significant cardioprotection in the REWIND trial, despite the trial population being lower risk than usual for cardiovascular outcome trials.
Just 31.5% of the 9901 people (46.3% women) with type 2 diabetes recruited to REWIND had overt cardiovascular disease; the remainder had an age of 60 years or older plus at least two of the risk factors of tobacco use, dyslipidemia, hypertension, and abdominal obesity.
Hertzel Gerstein (McMaster University and Hamilton Health Sciences, Ontario, Canada) and co-researchers presented the findings at the 79th ADA Scientific Sessions in San Francisco, California, USA, with simultaneous publication of two papers – the main analysis and an exploratory renal analysis – in The Lancet.
During a median follow-up of 5.4 years, the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes occurred in 12.0% of people taking dulaglutide versus 13.4% of those taking placebo, giving rates of 2.4 versus 2.7 per 100 person–years and a significant 12% reduction in risk with the GLP-1 receptor agonist.
In subgroup analyses, the effect of dulaglutide was the same regardless of whether patients had established cardiovascular disease and there were no differences based on any other patient characteristic, with the exception of their geographic region.
Dulaglutide treatment also significantly reduced the risk for microvascular disease, with rates of the composite microvascular outcome being 3.8 per 100 person–years, compared with 4.3 per 100 person–years in the placebo group, giving a significant 13% risk reduction.
However, study participants taking dulaglutide reported significantly more gastrointestinal adverse events than those taking placebo, at 47.4% versus 34.1%.
The exploratory renal analysis, examining a composite outcome of first occurrence of new macroalbuminuria, a sustained decline in estimated glomerular filtration rate of 30% or more from baseline, or need for chronic renal replacement therapy, also showed positive effects for dulaglutide.
This composite outcome occurred in 17.1% of people taking dulaglutide and 19.6% of those taking placebo, giving a significant 15% relative risk reduction with dulaglutide, with the effect being strongest for development of macroalbuminuria (HR=0.77).
At baseline, just over a third of patients had albuminuria, with less than 10% of all patients having macroalbuminuria.
Subodh Verma (University of Toronto, Ontario, Canada) and co-authors of a linked commentary note the results of the recent DECLARE-TIMI 58 trial, which provided evidence that sodium-glucose cotransporter 2 inhibition could prevent heart failure.
“If we are to reduce the burgeoning pump, pipes, and filter complications of diabetes, we will need to overcome clinical inertia, and embrace these disease-modifying therapies early, and preferably in combination,” they write. “The REWIND trial makes a strong case in this regard.”
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Lancet 2019; doi:10.1016/S0140-6736(19)31149-3
Lancet 2019; doi:10.1016/S0140-6736(19)31150-X
Lancet 2019; doi:10.1016/S0140-6736(19)31267-X
79th ADA Scientific Sessions; San Francisco, California, USA: 7–11 June 2019