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Metabolic & GLP-1 · Reference monograph

Long-acting exendin-4-based GLP-1 receptor agonist

Reference compound — not available from Purity Peptides. Shown for research context.

Overview

Efpeglenatide (HM11260C) is a long-acting incretin peptides.">GLP-1 receptor agonist created by the South Korean company Hanmi Pharmaceutical. It consists of a modified exendin-4 analogue conjugated, via a short polyethylene glycol linker, to a non-glycosylated human IgG4 Fc fragment, using Hanmi's LAPSCOVERY half-life extension platform.

Sanofi licensed the molecule in 2015 and ran a phase 3 programme, including the AMPLITUDE-O cardiovascular outcome trial, published in 2021. That study was notable for enrolling people with type 2 diabetes and either cardiovascular disease or chronic kidney disease, and for including participants using SGLT2 inhibitors, making it a reference point for cardiorenal outcome research. Sanofi later returned the rights to Hanmi, which has continued development in other settings, including obesity studies in Korea. Efpeglenatide is not approved by the FDA or EMA. For researchers it is of interest as an example of Fc-conjugate engineering and as a comparator in GLP-1 receptor pharmacology, especially regarding cardiovascular and kidney endpoints in clinical research.

Mechanism studied

  1. Efpeglenatide
  2. GLP-1 receptor
  3. Insulin & satiety signalling
  4. Cardiorenal endpoints

Efpeglenatide activates the GLP-1 receptor, a Gs-coupled class B G protein-coupled receptor, increasing intracellular cAMP. In beta cells this amplifies glucose-dependent insulin secretion, and in alpha cells it reduces glucagon release during hyperglycaemia. Like other agonists it slows gastric emptying and engages hypothalamic and brainstem satiety circuits. The Fc conjugate reduces renal clearance and supports neonatal Fc receptor-mediated recycling, prolonging exposure. The precise contribution of central versus peripheral receptor engagement to its effects has not been fully resolved. Mechanisms behind cardiorenal findings, whether metabolic, haemodynamic or anti-inflammatory, remain under investigation across the incretin peptides.">GLP-1 receptor agonist class.

Research highlights

  • 01Engineered by Hanmi Pharmaceutical using an exendin-4 analogue linked to an IgG4 Fc fragment through a PEG linker.
  • 02Licensed to Sanofi in 2015; rights were returned to Hanmi after the phase 3 programme.
  • 03The AMPLITUDE-O trial enrolled participants with type 2 diabetes plus cardiovascular or kidney disease, and permitted concurrent SGLT2 inhibitor use.
  • 04Subsequent work by Hanmi has explored obesity research in Korean populations.
  • 05Open questions include which mechanisms underlie cardiorenal endpoints for exendin-based versus human GLP-1-based agonists.

Latest published research

54 papers on PubMed →

  1. Exposure-driven tolerance modeling of efpeglenatide-induced nausea or vomiting using repeated time-to-event analysis: implications for dose-escalation strategies

    Seo J et al. · Frontiers in pharmacology · 2026 · PMID 42840589

  2. Potential Mediators of Efpeglenatide's Cardiovascular Benefit: An Exploratory Analysis of the AMPLITUDE-O Trial

    Raaschou-Oddershede D et al. · Diabetes, obesity & metabolism · 2026 Sep · PMID 42387302

  3. The Impact of GLP-1-Based Therapies on Cardiovascular Outcomes in Type 2 Diabetes: A Comprehensive Systematic Review and Network Meta-Analysis

    Chuang SM et al. · Diabetes, obesity & metabolism · 2026 Aug · PMID 42219271

  4. Preferred Glucagon-like Peptide-1 Receptor Agonists in Adults With Type 2 Diabetes and Established Cardiovascular Disease or High Cardiovascular Risk: A Network Meta-analysis of Randomized Trials

    Abomohsen M et al. · Canadian journal of diabetes · 2026 Aug · PMID 41967797

  5. Renal Outcomes of GLP-1 Receptor Agonists and Tirzepatide Across CKD Stages and Metabolic Phenotypes (Type 2 Diabetes and/or Overweight/Obesity): A Scoping Review

    Rico-Fontalvo J et al. · Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026 Apr · PMID 41848820

  6. Comparison of the renal outcomes of novel antidiabetic agents in patients with type 2 diabetes with chronic kidney disease: A systematic review and network meta-analysis of randomized controlled trials

    Lin R et al. · Diabetes, obesity & metabolism · 2026 Jan · PMID 41147324

  7. Population pharmacokinetics of efpeglenatide in individuals with obesity and with type 2 diabetes

    Choi S et al. · Frontiers in pharmacology · 2025 · PMID 41403449

  8. Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of 99,599 Patients

    Galli M et al. · Journal of the American College of Cardiology · 2025 Nov 18 · PMID 40892610

Live feed from PubMed (NCBI) for “Efpeglenatide”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.

Registered studies

5 on ClinicalTrials.gov →

From the public ClinicalTrials.gov registry for “Efpeglenatide”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.

Key references

  1. [1]Gerstein et al., 2021 — N Engl J Med 385:896–907
  2. [2]PubMed — reviews on efpeglenatide

FAQ

  • LAPSCOVERY is Hanmi Pharmaceutical's technology for extending peptide and protein half-life. It links an active peptide to a non-glycosylated human Fc fragment through a short PEG linker, reducing renal clearance and enzymatic degradation. Efpeglenatide was one of the first molecules developed on this platform.

  • No. Despite completing a phase 3 programme that included a cardiovascular outcome trial, efpeglenatide has not been approved by the FDA or EMA. It remains an investigational molecule studied for research purposes.

  • Both are based on exendin-4, the Gila monster venom peptide. Efpeglenatide uses a modified exendin-4 sequence conjugated to an Fc fragment, whereas exenatide is the unconjugated peptide. This conjugation is what gives efpeglenatide a much longer half-life.

FOR RESEARCH USE ONLY.Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.

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