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
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
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.