Efpeglenatide
Metabolic / DiabetesAlso known as: HM11260C, LAPS-Exendin-4
Mechanism
Efpeglenatide is a long-acting GLP-1 receptor agonist based on exendin-4 (the lizard-derived peptide behind exenatide). It is conjugated to an Fc fragment to extend its duration of action, allowing once-weekly or once-monthly dosing. The AMPLITUDE-O trial showed cardiovascular benefits in type 2 diabetes patients.
Technical detail
Efpeglenatide is a GLP-1 receptor agonist based on an exendin-4 backbone conjugated via a non-peptidyl linker to a human IgG4 Fc fragment (LAPS technology), dramatically extending half-life to support weekly or monthly dosing. It activates GLP-1R-mediated cAMP/PKA signaling for glucose-dependent insulin secretion, glucagon suppression, and gastric emptying delay. The AMPLITUDE-O trial demonstrated a 27% reduction in MACE in T2DM patients with CV risk.
Evidence
- moderate
(2025) — Springer Science and Business Media LLC — PMID: 10.7759/cureus.77089
Efpeglenatide significantly reduces HbA1c, fasting plasma glucose, and body weight in patients with type 2 diabetes and obesity. It offers cardiovascular and renal benefits with a favorable safety profile, including mild-to-moderate gastrointestinal side effects and a low risk of hypoglycemia.
- moderate
Gerstein HC et al. (2024) — Diabetes Obes Metab — PMID: 38116691
Secondary AMPLITUDE-O analysis suggested cardiovascular and renal benefit from efpeglenatide was preserved across multiple baseline CKD strata.
- strong
(2022) — American Diabetes Association — PMID: 10.2337/figshare.19640022.v1
Once-weekly efpeglenatide monotherapy significantly improved glycemic control and body weight in patients with type 2 diabetes, with HbA1c reductions from baseline of 1.2% to 1.7% and significant reductions in body weight and fasting plasma glucose.
- strong
Frias JP et al. (2022) — Diabetes Care — PMID: 35671039
Once-weekly efpeglenatide monotherapy improved glycemic control and supported acceptable short-term safety in adults with type 2 diabetes.
- strong
Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes.
Gerstein HC et al. (2021) — N Engl J Med — PMID: 34215025
AMPLITUDE-O showed efpeglenatide reduced major cardiovascular and renal events in high-risk adults with type 2 diabetes versus placebo.
- strong
Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes.
(2021) — MASSACHUSETTS MEDICAL SOC
Efpeglenatide reduced major adverse cardiovascular events (MACE) by 27% (HR 0.73, 95% CI 0.58-0.92) and renal outcome events by 32% (HR 0.68, 95% CI 0.57-0.79) compared to placebo in patients with type 2 diabetes at high risk for cardiovascular events.
- moderate
Pharmacokinetic and dose‐finding studies on efpeglenatide in patients with type 2 diabetes
(2020) — Wiley — PMID: 10.1111/dom.14032
Efpeglenatide, a GLP-1 receptor agonist, showed dose-proportional increases in serum concentrations, long half-life, and low peak-to-trough ratios. It reduced fasting and postprandial glucose levels and glycated hemoglobin with good tolerability in patients with type 2 diabetes.
- strong
(2020) — Wiley — PMID: 10.1111/dom.14223
The AMPLITUDE-O trial investigates the effect of efpeglenatide on cardiovascular outcomes in patients with type 2 diabetes with and without chronic kidney disease, with a primary outcome of major adverse CV events.