The AMPLITUDE-O Trial : CVOT of Efpeglenatide, a new potent, exendin-4-based weekly subcutaneous GLP-1 receptor agonist

<p>Efpeglenatide, is a novel, exendin-4-based weekly GLP-1 Receptor agonist that is administered subcutaneously, it effectively lowers glucose levels in people with T2DM.</p> <p>Recent guidelines have placed this class of agents as first-line glycemic-lowering therapy in people with baseline CVD, high risk for CVD, or chronic kidney disease (CKD)</p> <p>The AMPLITUDE-O Trial enrolled 4,076 adults with T2DM who had an HbA1c &gt;7.0% and either a baseline history of CVD (89.6%) or diabetic kidney disease (DKD) with an eGFR &lt;60 ml/min (31.6%).</p> <p>Baseline CVD was defined as a history of coronary artery disease (CAD), stroke, peripheral artery disease (PAD), or if they had at least one CVD risk factor and an eGFR between 25 to 59.9 ml/min per 1.73 m2 of body surface area in adults, men age ≥50 or women ≥55.12</p> <p>Notably, 21.8% of the participants had both CVD and DKD. All participants were already treated with standard of care, and they were also stratified based on the use of an SGLT-2 inhibitor (15.2%).</p> <p>The primary composite outcome was the first occurrence of a 3-point major adverse cardiovascular event (MACE), including nonfatal myocardial infarction, nonfatal stroke, or death from CV-related or undetermined causes.</p> <p>The key secondary outcomes were an expanded MACE composite outcome to include coronary revascularization or hospitalization for unstable angina and a composite renal outcome defined as a new onset of proteinuria (UACR &gt; 300 mg/g) and an increase in UACR ≥ 30% from baseline, a sustained decrease of eGFR ≥ 40% for at least 30 days, a sustained eGFR &lt; 15 ml/min per 1.73 m2 for at least 30 days, or any need for renal replacement therapy for at least 90 days.</p> <p>In this pivotal CVOT, there was a 27% reduction in the primary composite outcome in participants on efpeglenatide (4 or 6 mg weekly) (HR, 0.73; 95% CI, 0.58 - 0.92; p &lt; 0.007 for superiority) compared to placebo among persons with T2DM with CVD history or existing kidney disease</p> <p>Compared to the previous