Efpeglenatide

HM11260C, LAPS-Exendin-4, LAPSExd4 Analog; "Eppe" (reported Korean brand)

Metabolic & weight

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Efpeglenatide is a pharmaceutical GLP-1 receptor agonist that completed Phase 3 trials and a cardiovascular outcome trial. Global development was paused in 2020 when the licensing partner returned rights to the originator; the originator later completed a separate obesity programme in South Korea, where approval for obesity was reported in October 2026 †. It is not approved in the US, EU, UK, Australia or South Africa. Community use is essentially none documented.

Summary

Class: Long-acting GLP-1 receptor agonist: an exendin-4 analogue conjugated via a non-peptide linker to a human IgG4 Fc fragment (the "LAPS" long-acting platform), so the active part is a peptide carried by an antibody fragment
Mechanism: Activates the GLP-1 receptor to boost glucose-dependent insulin release, suppress glucagon, slow gastric emptying and reduce appetite; the Fc carrier extends half-life to allow weekly or less frequent dosing
Routes studied: Subcutaneous injection, once weekly (also once-monthly dosing explored in early trials)
Half-life: Roughly 6–7 days (supports weekly dosing) †
Storage: Investigational/approved product: refrigerated pens; follow label. Not supplied as lyophilised powder
Regulatory status: Reported approved in South Korea for obesity (2026) †; not approved elsewhere

Doses are as reported in studies or by the community — never recommendations.

1What it is

Efpeglenatide is an exendin-4-based peptide (the same lizard-derived sequence family as exenatide and lixisenatide) attached to an antibody Fc fragment through a flexible chemical linker. The construct was designed so the peptide survives in the bloodstream for a week or more rather than hours. It was developed in South Korea and licensed to a large pharmaceutical company in 2015, which ran a full Phase 3 programme (AMPLITUDE) in type 2 diabetes, including a dedicated cardiovascular outcome trial. In 2020 the licensee returned the rights, and no regulatory filing was made in the US or EU. The originator continued development for obesity in Korea, and Korean press in October 2026 reported domestic approval as the country's first home-developed GLP-1 obesity drug †.

It is included here because it has one of the largest published cardiovascular datasets of any GLP-1 that never reached Western markets, and because the "Fc-fused peptide" design is increasingly common in pipeline compounds.

2How it's thought to work

The pharmacology is standard GLP-1 receptor agonism (see Semaglutide, profile #3, for the general mechanism):

Glucose-dependent insulin secretion and reduced glucagon from the pancreas.

Slowed gastric emptying and reduced appetite via brainstem and hypothalamic GLP-1 receptors.

Because exendin-4-based are not broken down by DPP-4 and the Fc fragment prevents kidney filtration and recycles through the FcRn pathway, the exposure is flat across the week rather than peaking after each injection.

An exendin-based GLP-1 agonist attached to an antibody fragment for weekly dosing. Showed cardiovascular and kidney benefit in trial but was not brought to market.Schematic — not to scale

3What the research shows

Cardiovascular outcomes in type 2 diabetes

AMPLITUDE-O randomised 4,076 people with type 2 diabetes and either cardiovascular disease or kidney disease plus another risk factor to efpeglenatide 4 mg or 6 mg weekly or placebo, followed for a median of 1.8 years. Major adverse cardiovascular events were reduced by 27% (hazard ratio 0.73), and a composite kidney outcome was reduced by 32% (Gerstein 2021, NEJM). The trial was stopped early for commercial reasons after the rights were returned, but it had already accrued enough events to show superiority, not just non-inferiority. [1]

Glycaemic control

The AMPLITUDE-M (monotherapy), AMPLITUDE-D (vs dulaglutide), AMPLITUDE-L (on basal insulin) and AMPLITUDE-S (on sulfonylurea) trials reported HbA1c reductions in the range of roughly 1.2–1.6 percentage points, broadly comparable to other weekly GLP-1 ; the head-to-head against dulaglutide reported non-inferiority with numerically greater reductions at higher doses (Frias 2022, Diabetes Care; Del Prato 2022, Diabetes Care) †. [3][4]

Weight loss

In type 2 diabetes trials weight loss was modest (around 2–3 kg vs placebo). A Korean Phase 3 trial in people with obesity without diabetes reported mean weight loss of about 9.75% at 40 weeks according to press coverage of the approval (2026) †.

Early-phase pharmacology

Phase 2 work showed dose-dependent HbA1c and weight effects with weekly and monthly dosing, including in people with obesity (Rosenstock 2019, Diabetes Care). [2]

4Reported side effects and interactions

Literature-reported

Gastrointestinal effects typical of the class: nausea, vomiting, diarrhoea and constipation, mostly during titration. Injection-site reactions were more common than with some peptide-only GLP-1 , plausibly related to the Fc construct. Anti-drug antibodies were detected in a proportion of participants; their clinical significance was reported as limited †. Pancreatitis and gallbladder events occurred at low rates in both arms.

Community-reported

essentially none documented.

Theoretical. class warnings for thyroid C-cell tumours in rodents, retinopathy complications in people with existing diabetic retinopathy, and acute kidney injury with dehydration apply to all GLP-1 agonists.

Interactions. additive hypoglycaemia with insulin or sulfonylureas; slowed absorption of oral medicines.

Markers researchers commonly monitor

Follow the GLP-1 class pattern (see profile #3):

Marker	Why it's watched
HbA1c and fasting glucose	primary efficacy marker; hypoglycaemia risk with insulin or sulfonylureas.
eGFR and creatinine	AMPLITUDE-O showed kidney benefit, but dehydration from GI effects can transiently worsen kidney function.
Lipase/amylase	only if abdominal pain develops.
Body weight and body composition	lean mass loss is a class effect.
Resting heart rate	GLP-1 agonists raise it by a few beats per minute.
Anti-drug antibodies	measured in trials because of the Fc construct; not a routine clinical test.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Supplied only as a finished pharmaceutical product (pre-filled pens) in trials and in Korea. No is involved and no form circulates. The calculator does not apply to this compound.

6Commonly studied alongside

Compared head-to-head with dulaglutide (profile #61) and conceptually with exenatide (the parent sequence) and semaglutide (#3). Studied on top of metformin, basal insulin and SGLT2 inhibitors. No community co-use is documented.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; no NDA filed after rights were returned in 2020
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport (WADA)	GLP-1 agonists are not on the Prohibited List as of 2026 †

8Open questions

Will the cardiovascular benefit shown in AMPLITUDE-O be replicated in the Korean obesity population, and will any filing be made outside Korea?
Does the Fc-fusion design change long-term immunogenicity compared with fatty-acid-acylated GLP-1 ?
How does weight loss compare with semaglutide or tirzepatide at equivalent exposure? No head-to-head data exist.

9References

1Gerstein HC et al. (2021). Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes (AMPLITUDE-O). NEJM. PubMed · DOI
2Rosenstock J et al. (2019). Efpeglenatide, a long-acting GLP-1 receptor agonist, in patients with type 2 diabetes inadequately controlled on diet and exercise or metformin: a phase 2 trial. Diabetes Care. PubMed
3Frias JP et al. (2022). Efficacy and safety of once-weekly efpeglenatide monotherapy versus placebo in type 2 diabetes: the AMPLITUDE-M randomized controlled trial. Diabetes Care. PubMed · DOI
4Del Prato S et al. (2022). Efficacy and safety of efpeglenatide versus dulaglutide in type 2 diabetes (AMPLITUDE-D). Diabetes Care [verify journal]. PubMed
5Lakshmanan MC et al. (2021). Cardiovascular and renal outcomes with efpeglenatide across baseline kidney function: a prespecified analysis of AMPLITUDE-O. Lancet Diabetes Endocrinol [verify]. PubMed
6Korean regulatory approval of efpeglenatide for obesity, press reports October 2026 [verify primary source]. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

31 Oct 2026Profile published — awaiting medical review

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