Efpeglenatide

Fat LossInvestigational long-acting GLP-1 receptor agonistEmerging

Efpeglenatide is an investigational long-acting GLP-1 receptor agonist. Efpeglenatide is an exendin-4 analog conjugated to a human immunoglobulin Fc fragment through a flexible linker. The Fc domain engages the neonatal Fc receptor recycling pathway, which greatly extends half-life and supports weekly or less frequent dosing, while the exendin portion provides GLP-1 receptor agonism.

Calculate Dose

For research use only.

Key Facts

CAS: —
Molecular Weight (MW): —
Half-life: 135–180 hours (geometric mean) in phase 2 studies in type 2 diabetes
FDA status: Investigational New Drug (IND)
Evidence level: Clinical Trial Evidence
Human dose established: Yes
Administration Route: Subcutaneous
Frequency: Once weekly (once-monthly dosing was tested in phase 2)
Last updated: Nov 7, 2026
Reviewed: Nov 7, 2026

Research summary

Long-acting exendin-based GLP-1 receptor agonist studied for type 2 diabetes and cardiovascular and renal outcomes. Not FDA-approved.

Research evidence

Regulatory review (FDA label)None in reviewed sources
Controlled human trials4 reviewed sources
Early or uncontrolled human studiesNone in reviewed sources
Lab & animal studiesNone in reviewed sources

How it works

Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.

Peptide Library's Efpeglenatide profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.

Efpeglenatide dosage evidence

Efpeglenatide has no approved dosage. Human dosing comes from the AMPLITUDE phase 3 programme in type 2 diabetes, which tested 2, 4 or 6 mg injected under the skin once a week; in the AMPLITUDE-O outcomes trial, 4 or 6 mg weekly lowered the risk of major cardiovascular events against placebo. Four phase 3 trials are listed on ClinicalTrials.gov as terminated by sponsor decision, not for safety reasons, and the drug was not approved.

Clinical Trial Evidence

Dosage evidence summary for Efpeglenatide
Human dosing established	Yes
Studied dose range	2–6 mg once weekly in phase 3 trials
Route	Subcutaneous
Frequency	Once weekly (once-monthly dosing was tested in phase 2)
Duration studied	Up to 56 weeks of treatment; median follow-up 1.81 years in AMPLITUDE-O
Titration	In the AMPLITUDE trial against dulaglutide, participants started at 2 mg weekly and stepped up every 2 weeks to 4 mg or 6 mg.
Half-life	135–180 hours (geometric mean) in phase 2 studies in type 2 diabetes
Evidence level	Clinical Trial Evidence
Last reviewed	2026-11-07

Research-reported dosing

Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.

Research-reported dosing for Efpeglenatide, one row per studied regimen
Study / context	Population	Dose	Route	Frequency	Duration	Outcome studied	Source
AMPLITUDE-O — phase 3 cardiovascular and kidney outcomes (NCT03496298)Clinical trial · Randomized, placebo-controlled phase 3 outcomes trial	Adults with type 2 diabetes and cardiovascular disease or kidney disease plus a risk factor (n=4,076)	4 mg or 6 mg	Subcutaneous	Once weekly	Median follow-up 1.81 years	Major cardiovascular events in 7.0% with efpeglenatide against 9.2% with placebo (hazard ratio 0.73); composite kidney outcome in 13.0% against 18.4% (hazard ratio 0.68)	Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes. N Engl J Med. 2021.
AMPLITUDE-M — phase 3 monotherapyClinical trial · Randomized, double-blind, placebo-controlled phase 3 trial	Adults with type 2 diabetes on diet and exercise alone (n not stated in the indexed abstract)	2, 4 or 6 mg	Subcutaneous	Once weekly	Up to 56 weeks (primary endpoint at week 30)	HbA1c fell from 8.1% to 6.9%, 6.6% and 6.4% at week 30 with 2, 4 and 6 mg; each dose beat placebo	Efficacy and Safety of Once-Weekly Efpeglenatide Monotherapy Versus Placebo in Type 2 Diabetes: The AMPLITUDE-M Randomized Controlled Trial. Diabetes Care. 2022.
Phase 2 single-dose and repeated-dose studiesClinical trial · Two randomized, double-blind, placebo-controlled phase 2 trials	Adults with type 2 diabetes (n=48 single-dose; n=71 repeated-dose)	Single dose 2–100 mcg/kg; repeated 1, 2 or 4 mg weekly or 8, 12 or 16 mg monthly	Subcutaneous	Single dose, once weekly or once monthly	Single dose; 8 weeks (weekly) or 9 weeks (monthly)	Dose-proportional exposure; repeated doses lowered HbA1c against placebo; gastrointestinal effects most common	Pharmacokinetic and dose-finding studies on efpeglenatide in patients with type 2 diabetes. Diabetes Obes Metab. 2020.
AMPLITUDE trial versus dulaglutide — terminated (NCT03684642)Clinical trial · Phase 3 randomized trial, terminated	Adults with type 2 diabetes on metformin (n=908)	Started at 2 mg and raised every 2 weeks to 4 mg or 6 mg (compared with dulaglutide 1.5 mg)	Subcutaneous	Once weekly	Up to 56 weeks	Terminated; the registry reason is "Sponsor decision to cancel TRIAL, not related to safety concern". Results are posted on ClinicalTrials.gov and not summarised here	NCT03684642 — Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin

Where sources disagree

Efpeglenatide was not approved. Four phase 3 efpeglenatide records on ClinicalTrials.gov, including AMPLITUDE-O (NCT03496298), are listed as terminated by sponsor decision "not related to safety concern". AMPLITUDE-O still reported its primary outcome.
Efpeglenatide is an exendin-based GLP-1 receptor agonist. Its milligram doses are not interchangeable with exenatide, which is dosed in micrograms, or with other weekly GLP-1 drugs.

Efpeglenatide dosage in published studies and labels →

Science

Mechanism of Action

Efpeglenatide is an exendin-4 analog conjugated to a human immunoglobulin Fc fragment through a flexible linker. The Fc domain engages the neonatal Fc receptor recycling pathway, which greatly extends half-life and supports weekly or less frequent dosing, while the exendin portion provides GLP-1 receptor agonism.

Studies

Research statistics

47 PubMed publications · 29.8% human clinical research · 13 registered trials

Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted

Regulatory & research status

Efpeglenatide has been studied under an Investigational New Drug application. It is not approved for marketing.

Regulatory and research status for Efpeglenatide
FDA status	Investigational New Drug (IND)
Research status	Investigational; clinical development reported
Availability	Research-Only
WADA (sport)	Unknown / Not Listed
Library classification	Clinical Trial

How FDA approval, compounding and research-only status differ

Benefits

—

Efpeglenatide side effects

No side effects listed yet for this entry.

Storage & stability

This compound is not supplied as a powder to be mixed, so the freeze-dried powder and reconstitution handling described for research peptides does not apply. Storage conditions are product-specific: follow the label or packaging of the product itself.

Efpeglenatide: frequently asked questions

What is Efpeglenatide?

Long-acting exendin-based GLP-1 receptor agonist studied for type 2 diabetes and cardiovascular and renal outcomes. Not FDA-approved.

How does Efpeglenatide work?

Is Efpeglenatide FDA approved?

No. Efpeglenatide is investigational: it is in clinical development and has not been approved by the FDA for any indication. Investigational status means trials are ongoing or complete but regulatory review has not resulted in approval, and efficacy and safety are still being established.

What peptides are similar to Efpeglenatide?

Compounds most often compared with Efpeglenatide include Tirzepatide, VK2735, Ecnoglutide and Semaglutide. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.

References

Related research, comparisons & guides

Related peptides

Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Nov 7, 2026 · Version 2

This Efpeglenatide profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error

Track Efpeglenatide research, inventory and reconstitution in the free Peptide Library app. Get the app for iOS or Android →