AMPLITUDE-O: Efpeglenatide offers cardiorenal protection in type 2 diabetes
medwireNews: Efpeglenatide provides significant cardiovascular and renal protection in people with type 2 diabetes at high risk for cardiorenal events, show the findings of the AMPLITUDE-O trial.
The positive result comes despite the cardiovascular outcomes trial closing after the accrual of 314 primary outcome events, rather than the intended 330, due to the sponsor’s decision to end funding.
The trial was conducted at 344 sites in 28 countries and enrolled people with type 2 diabetes who had established cardiovascular disease (89.6%), renal disease plus other cardiovascular risk factors (31.6%), or had both cardiovascular and renal disease (21.8%).
During a median follow-up of 1.81 years, 9.2% of the 1359 participants randomly assigned to receive placebo had a primary outcome event – a major adverse cardiovascular event (MACE), defined as nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or undetermined causes.
The rate among the 2717 participants assigned to receive the glucagon-like peptide (GLP)-1 receptor agonist efpeglenatide at a weekly dose of 4 or 6 mg was 7.0%, report Hertzel Gerstein (McMaster University, Hamilton, Ontario, Canada) and co-researchers.
This equated to a 27% risk reduction and made it statistically noninferior and also superior to placebo.
“Thus, an estimated 46 similar patients would need to be treated with efpeglenatide for 1.8 years to prevent one MACE,” the team writes.
The positive effect of efpeglenatide was seen regardless of factors such as age, sex, duration of diabetes, baseline glycated hemoglobin level, and whether participants were taking a sodium-glucose cotransporter (SGLT)2 inhibitor, which was the case for 15.2% of the cohort at baseline.
This last result indicates “that the beneficial cardiovascular effects of efpeglenatide may be independent of those of an SGLT2 inhibitor,” write the researchers in The New England Journal of Medicine.
An exploratory analysis suggested the presence of a dose–response effect, with the 4 and 6 mg efpeglenatide doses being associated with a nonsignificant 18% and a significant 35% risk reduction versus placebo, respectively.
Efpeglenatide was also associated with a 32% reduction in the risk for the secondary endpoint of a composite renal outcome, comprising incident macroalbuminuria, plus at least a 30% increase in the urinary albumin-to-creatinine ratio, a reduction of estimated glomerular filtration rate (eGFR) by at least 40% for 30 days or longer, renal-replacement therapy for at least 90 days, or an eGFR below 15 mL/minute per 1.73 m2 for 30 days or more.
Gerstein and team write: “[T]he fact that these findings accrued with a long-acting exendin-4–based GLP-1 receptor agonist suggests that the cardiovascular benefits of this class of agents are not restricted to GLP-1 receptor agonists that are structurally similar to human GLP-1.”
The researchers also presented their findings at the virtual ADA 81st Scientific Sessions.
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