AMPLITUDE-O: efpeglenatide becomes the first long-acting exendin-based GLP-1 receptor agonist to show CV and renal benefits in type 2 diabetes
This cardiovascular outcomes trial evaluated efpeglenatide in 4076 participants with type 2 diabetes and either a history of cardiovascular (CV) disease or current kidney disease plus at least one other cardiovascular risk factor. Participants were randomly assigned 1:1:1 to receive weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg or placebo.
The primary outcome was the first major adverse cardiovascular event (MACE; a composite of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular or undetermined causes). During a median follow-up of 1.81 years, efpeglenatide decreased the incidence of MACE by 27% (HR, 0.73; 95% CI, 0.58-0.92; P = 0.007 for superiority).
A composite renal outcome event (a decrease in renal function or macroalbuminuria) was reduced by 32% in patients treated with efpeglenatide (HR, 0.68; 95% CI, 0.57-0.79; P<0.001).
For the first time, a long-acting exendin analogue has shown cardiovascular and renal benefits in patients with type 2 diabetes, defying the concept that, within the GLP-1 (glucagon-like peptide 1) receptor agonists family, only human GLP-1 analogues were able to provide cardiovascular protection.
As with other GLP-1 receptor agonists, efpeglenatide significantly reduces several risk factors for cardiovascular and renal disease such as HbA1c and blood pressure, which the authors commented as possible pathways for protecting the heart and the kidneys, drawing on evidence from published mediation analysis of other GLP-1 receptor agonists that have suggested their cardiorenal benefits may be partially mediated by effects on HbA1c, blood pressure; and a meta-regression analysis of GLP-1 receptor agonists suggested a linear relation between lowering of HbA1c levels and reduced risks of MACE.