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

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. 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) The AMPLITUDE-O Trial enrolled 4,076 adults with T2DM who had an HbA1c >7.0% and either a baseline history of CVD (89.6%) or diabetic kidney disease (DKD) with an eGFR <60 ml/min (31.6%). 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 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%). 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. 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 > 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 < 15 ml/min per 1.73 m2 for at least 30 days, or any need for renal replacement therapy for at least 90 days. 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 < 0.007 for superiority) compared to placebo among persons with T2DM with CVD history or existing kidney disease Compared to the previous CVOTs of GLP-1 RAs, the AMPLITUDE-O Trial included participants who were at a higher risk for CVD and had more cases of kidney disease The significant benefits were also observed in the expanded MACE composite outcome, a MACE or death from non-cardiovascular causes and composite renal outcome. Benefits were greater in those who had baseline CVD, were on baseline metformin, were obese with body mass index (BMI) > 31.9 kg/m2 and had a baseline eGFR < 71.5 ml/min per 1.73 m2 This trial, with an exendin-4-based, weekly GLP-1 RA, further reinforces the expanding and robust database beyond the GLP-1 RAs that have a similar structure to human GLP-1 as powerful glycemic-lowering and weight-loss agents as well as effective in reducing CV and renal adverse event risks. Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ­­­STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.