Efpeglenatide
Hanmi's once-weekly GLP-1 receptor agonist, an exendin-4 analog linked to an antibody Fc fragment. Under Sanofi it cut major cardiovascular events by 27% in the 4,076-person AMPLITUDE-O trial; back with Hanmi, a Korean obesity Phase 3 showed 9.75% weight loss at 40 weeks vs 0.95% on placebo. Under Korean MFDS review as of October 2026.
Efpeglenatide is a weekly shot from the Korean drugmaker Hanmi that works like Ozempic. In a big study of people with type 2 diabetes, it lowered the chance of heart attacks, strokes and heart-related deaths by about a quarter. In a Korean weight-loss study, people lost about 10% of their weight in 40 weeks. Korea is still reviewing it, and it is not approved anywhere yet.
What is Efpeglenatide?
Efpeglenatide (HM11260C; Korean brand name 에페, written Eppe or Epe in English-language press) is a once-weekly GLP-1 receptor agonist from Hanmi Pharmaceutical of South Korea. Unlike semaglutide or liraglutide, which are modified versions of human GLP-1, efpeglenatide is built on exendin-4, the Gila-monster peptide behind exenatide. A single-amino-acid-modified exendin-4 is joined through a small 3.4-kDa polyethylene glycol linker to the Fc fragment of a human IgG4 antibody, using Hanmi's LAPSCOVERY platform. The Fc fragment makes the molecule large and slowly cleared, giving a half-life of roughly 6 to 7.5 days (135 to 180 hours). The drug has an unusual history. Sanofi licensed it in November 2015 and ran a global Phase 3 program in type 2 diabetes. Its cardiovascular outcome trial, AMPLITUDE-O (4,076 people with type 2 diabetes and cardiovascular or kidney disease), found that weekly efpeglenatide cut major adverse cardiovascular events by 27% (hazard ratio 0.73) and a kidney composite by 32% versus placebo over a median 1.8 years, published in the New England Journal of Medicine in 2021. Sanofi nonetheless told Hanmi in May 2020 that it would return the rights and confirmed the decision that September; three other Phase 3 trials were stopped early for funding reasons, not safety or efficacy. Hanmi then repositioned the drug for obesity in Korea. In a Phase 3 trial of 448 Korean adults with obesity and no diabetes, mean weight change at the week-40 primary endpoint was -9.75% on efpeglenatide versus -0.95% on placebo (Hanmi reported a least-squares mean difference of 8.13 percentage points), and 79.4% versus 14.5% lost at least 5%. Hanmi filed with Korea's Ministry of Food and Drug Safety (MFDS) on 17 December 2025 under the Global Innovative Product Fast Track (GIFT). As of early October 2026 the application is under MFDS review. If approved, it would be the first GLP-1 obesity drug developed by a Korean company. It is not approved anywhere and has no US filing.
What Efpeglenatide Is Investigated For
Efpeglenatide is unusual among unapproved GLP-1 drugs in having a completed, positive cardiovascular outcome trial, but that evidence comes from type 2 diabetes at doses of 4 to 6 mg weekly. AMPLITUDE-O showed a 27% reduction in major adverse cardiovascular events and a 32% reduction in a kidney composite, with a clear dose response (6 mg did better than 4 mg). The obesity case rests on Hanmi's Korean Phase 3: 9.75% mean weight loss at 40 weeks versus 0.95% on placebo in 448 adults without diabetes, with relatively low GI side-effect rates (nausea 16.7% vs 5.4%). That weight loss is well below what semaglutide 2.4 mg and tirzepatide produce in their pivotal trials, and the Korean data are a company-reported topline that has not been published in a peer-reviewed journal. Earlier Sanofi trials established glycemic efficacy: in AMPLITUDE-M, HbA1c fell 0.5 to 1.0 percentage points more than placebo at 30 weeks, and in AMPLITUDE-D efpeglenatide was non-inferior to dulaglutide 1.5 mg. Hanmi is now running a Korean Phase 3 in type 2 diabetes (add-on to metformin and dapagliflozin), aiming for a diabetes indication around 2028. The honest framing: a modest weight-loss drug with unusually strong outcome data in diabetes, likely to compete in Korea on access and supply rather than on peak efficacy.
History & Discovery
Efpeglenatide came out of Hanmi Pharmaceutical's LAPSCOVERY program, which links peptides to an antibody Fc fragment to stretch their duration of action. Early names included LAPS-Exendin and LAPS-exendin-4. The first healthy-volunteer study began in 2010 (NCT01093729), and Phase 2 trials from 2011 to 2014 tested weekly, every-two-weeks and even once-monthly dosing in type 2 diabetes and obesity. In November 2015 Hanmi licensed the drug to Sanofi as a diabetes treatment. Sanofi's AMPLITUDE Phase 3 program enrolled about 6,000 patients across roughly 300 centers in 30 countries. In May 2020 Sanofi told Hanmi it would return the rights, and it confirmed the decision in September 2020. Three AMPLITUDE trials were cut short for funding reasons, but the cardiovascular outcome trial AMPLITUDE-O was reported in the New England Journal of Medicine in 2021, showing a 27% reduction in major adverse cardiovascular events. Hanmi then pivoted the drug to obesity in Korea. The MFDS approved a Phase 3 trial in October 2023, the first participant was enrolled in January 2024, and the week-40 primary endpoint was met (topline announced 27 October 2025). The MFDS designated efpeglenatide for GIFT fast-track review on 27 November 2025, and Hanmi filed for approval on 17 December 2025. A Korean Phase 3 in type 2 diabetes, testing the drug on top of metformin and dapagliflozin, was cleared on 21 January 2026 and began enrolling in April. Hanmi also signed a supply agreement with Laboratorios Sanfer for Mexico. Efpeglenatide is the first product of Hanmi's H.O.P. (Hanmi Obesity Pipeline) project, which also includes HM17321, a urocortin-2 analog licensed to Genentech.
How It Works
Efpeglenatide copies the action of GLP-1, a gut hormone that signals fullness, slows stomach emptying and helps the pancreas release insulin when blood sugar is high. It is based on exendin-4, a GLP-1-like peptide from Gila monster saliva, and is attached to a piece of an antibody so the body clears it slowly. One shot lasts about a week.
Efpeglenatide is a GLP-1 receptor agonist made by linking a single-amino-acid-modified exendin-4 to the Fc region of human immunoglobulin G4 through a 3.4-kDa mini-polyethylene glycol linker (Hanmi's LAPSCOVERY, or long-acting peptide/protein discovery, platform). Exendin-4 is naturally resistant to DPP-4, the enzyme that destroys human GLP-1 within minutes, and the Fc conjugation slows clearance. In type 2 diabetes studies, peak levels came 48 to 144 hours after injection, half-life was 135 to 180 hours, and the peak-to-trough ratio was only 1.3 to 1.4 with weekly dosing (5.9 to 12.9 with monthly dosing), which is why weekly dosing became the standard. A pooled population-pharmacokinetic analysis across obesity and diabetes studies found roughly dose-proportional exposure and no need for routine dose adjustment by body weight. Downstream effects are those of the GLP-1 class: glucose-dependent insulin secretion, glucagon suppression, slower gastric emptying and reduced appetite via brainstem and hypothalamic circuits. In a Phase 1b study, 6 mg weekly slowed gastric emptying about as much as liraglutide 1.8 mg daily. Hanmi's in-vitro work, cited in its clinical papers, reports faster dissociation from the GLP-1 receptor and less receptor internalization than other GLP-1 drugs; that is a company hypothesis for tolerability, not a demonstrated clinical difference. The cardiovascular benefit in AMPLITUDE-O was dose-dependent: the 6 mg dose reduced major adverse cardiovascular events by 35% (hazard ratio 0.65) while 4 mg gave a non-significant 18% reduction. A 2026 mediation analysis found that changes in LDL cholesterol and urinary albumin, not weight loss, statistically explained about 30% of the effect, leaving most of it unexplained by measured variables.
Evidence Snapshot
Human Clinical Evidence
Moderate and unusually deep for a drug that has never been approved. Sanofi-era data: Phase 2 dose-finding in type 2 diabetes and obesity (including every-two-weeks and monthly schedules), AMPLITUDE-M (406 participants) and AMPLITUDE-D, -L and -S (stopped early for funding reasons), and AMPLITUDE-O (4,076 participants, NEJM 2021: MACE hazard ratio 0.73; kidney composite 0.68). Hanmi-era data: a Korean Phase 3 in 448 adults with obesity (topline: -9.75% vs -0.95% at 40 weeks, 64-week follow-up completed March 2026 but not yet published) and a Korean Phase 3 in type 2 diabetes recruiting since April 2026. The obesity evidence is company-reported and Korea-only.
Animal / Preclinical
Preclinical comparisons with liraglutide and dulaglutide have been presented mainly as Hanmi conference abstracts rather than full papers. The human dataset is far larger than the published animal work.
Mechanistic Rationale
Strong. GLP-1 receptor agonism is well validated, exendin-4 is the basis of the approved drug exenatide, and Fc fusion as a half-life strategy is proven by dulaglutide. The only open mechanistic claim is Hanmi's receptor-kinetics tolerability hypothesis.
Research Gaps & Open Questions
What the current literature has not yet settled about Efpeglenatide:
- 01Peer-reviewed publication of the Korean obesity Phase 3, including the 64-week results, dropout rates and the exact dose.
- 02Whether the cardiovascular and kidney benefits seen in type 2 diabetes at 4 to 6 mg extend to people with obesity but no diabetes.
- 03Efficacy and tolerability of the obesity dose outside Korea.
- 04Whether Hanmi's proposed receptor-kinetics advantage translates into better tolerability than semaglutide at matched weight loss; no head-to-head trial exists.
- 05Most of AMPLITUDE-O's cardiovascular benefit is not explained by the measured risk factors; the mechanism is unresolved.
- 06Long-term body-composition data (fat vs lean mass) with the obesity dose.
Forms & Administration
Once-weekly subcutaneous injection. The Korean filing was for an auto-injector, and Hanmi has said it is developing prefilled-syringe and multi-dose pen formats. Earlier trials also tested every-two-weeks (6 and 8 mg) and once-monthly (8 to 16 mg) schedules, but weekly dosing was carried forward. Not available outside Hanmi trials while the Korean application is under review.
Dosing & Protocols
The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.
Typical Range
Investigational only. Sanofi's diabetes trials used 2, 4 and 6 mg weekly, and AMPLITUDE-O used 4 or 6 mg weekly. The Phase 2 obesity trial used 4 or 6 mg weekly or 6 or 8 mg every two weeks. Korean press reported a 10 mg weekly target dose for the obesity Phase 3; the dose is not listed in the trial registry, and Korean prescribing information has not been issued.
Frequency
Once weekly by subcutaneous injection.
Timing Considerations
No specific timing requirements: can be administered at any time of day, with or without food, and is not tied to exercise timing. Consistency matters more than the specific clock — dose at roughly the same time each day (or same day each week, for weekly protocols) to keep exposure steady.
Cycle Length
The Korean obesity Phase 3 had its primary endpoint at 40 weeks and continued to 64 weeks. Like other obesity drugs, efpeglenatide is intended for long-term use; cycling has not been studied.
Protocol Notes
These are trial doses, not use guidance. Efpeglenatide is investigational and should only be used inside a clinical trial or, if approved in Korea, under a clinician's prescription and supervision. Trials used stepwise dose escalation to limit GI side effects, as is standard for the class. The Phase 2 program showed that every-two-weeks and monthly schedules were possible, but monthly dosing produced much larger peak-to-trough swings and less gastric slowing, and weekly dosing was carried forward. Material sold online under the efpeglenatide or HM11260C name is not the investigational product.
Efpeglenatide is not approved by any regulator; doses come from published trials and Korean press reports of Hanmi's protocol.
Timeline of Effects
Onset
In type 2 diabetes, fasting and post-meal glucose fell within the first week after a single dose and stayed below baseline for at least three weeks. Weight loss builds over months: in the 20-week Phase 2 obesity trial, placebo-adjusted loss reached 6.3 to 7.2 kg.
Peak Effect
The Korean Phase 3 reported 9.75% mean weight loss at week 40. The trial ran to week 64, but Hanmi has not published whether weight loss continued or plateaued after week 40.
After Discontinuation
With a half-life of 135 to 180 hours, most of the drug clears within about five weeks of the last dose. Discontinuation has not been studied specifically, but weight regain after stopping is typical of GLP-1 drugs.
Common Questions
What is efpeglenatide (Eppe)?
Efpeglenatide is a once-weekly GLP-1 receptor agonist injection developed by Hanmi Pharmaceutical. Its Korean brand name is 에페, romanized as Eppe or Epe. It combines an exendin-4 analog (the same parent peptide as exenatide) with an antibody Fc fragment that keeps it in the body for about a week. Hanmi filed it with Korea's MFDS for obesity in December 2025, and the application is under review.
How does efpeglenatide compare to semaglutide (Wegovy, Ozempic)?
No head-to-head trial exists. In Hanmi's Korean Phase 3, efpeglenatide produced 9.75% mean weight loss at 40 weeks (0.95% on placebo). Semaglutide 2.4 mg produced 14.9% at 68 weeks in STEP 1 (2.4% on placebo). The trials differ in population, length and analysis, so the gap is not exact, but efpeglenatide's weight loss is clearly more modest. Both drugs have cardiovascular outcome data: efpeglenatide cut major cardiovascular events by 27% in people with type 2 diabetes (AMPLITUDE-O), while semaglutide cut them by 20% in people with obesity and heart disease but no diabetes (SELECT). Efpeglenatide's reported GI side-effect rates in the Korean trial (nausea 16.7%, vomiting 11.7%) were relatively low, but its doses and weight loss were also lower, so this is not evidence of better tolerability at equal effect.
How does efpeglenatide compare to tirzepatide (Mounjaro, Zepbound)?
Tirzepatide activates both GLP-1 and GIP receptors and produced 20.9% weight loss at 72 weeks on 15 mg in SURMOUNT-1. Efpeglenatide activates GLP-1 receptors only and produced 9.75% at 40 weeks in its Korean Phase 3. They have never been compared directly, but on current evidence tirzepatide is the much more potent weight-loss drug. Efpeglenatide's distinguishing evidence is its cardiovascular outcome trial in type 2 diabetes.
Why did Sanofi give efpeglenatide back to Hanmi?
Not because the drug failed. Sanofi notified Hanmi in May 2020 that it would return the rights and confirmed in September 2020 that it was stopping clinical development of efpeglenatide. Three AMPLITUDE Phase 3 trials (D, L and S) were stopped early for funding reasons, which the investigators state was not because of safety or efficacy concerns. AMPLITUDE-O was published in 2021 and was positive.
When will efpeglenatide be available?
Only Korea has an application under review. Hanmi filed with the MFDS on 17 December 2025 under the GIFT fast-track program, and as of early October 2026 no approval has been announced. Hanmi has a distribution agreement with Laboratorios Sanfer for Mexico, where Sanfer is responsible for seeking approval. There is no US or European filing, and no current US trial.
What makes efpeglenatide structurally different?
Most weekly GLP-1 drugs (semaglutide, tirzepatide) attach a fatty acid so the peptide rides on albumin. Efpeglenatide instead links its exendin-4 analog to an antibody Fc fragment through a small PEG linker, which makes it a much larger molecule that is cleared slowly. Dulaglutide (Trulicity) uses a related idea, fusing a GLP-1 analog to an IgG4 Fc. Hanmi has reported laboratory data suggesting efpeglenatide dissociates from the GLP-1 receptor faster and causes less receptor internalization than other GLP-1 drugs, but whether that matters clinically has not been tested.
Does efpeglenatide work in type 2 diabetes?
Yes, in Sanofi's trials. In AMPLITUDE-M (diet and exercise only), HbA1c at 30 weeks fell from 8.1% to 6.9%, 6.6% and 6.4% on 2, 4 and 6 mg. In AMPLITUDE-D, 4 mg and 6 mg were non-inferior to dulaglutide 1.5 mg at 56 weeks. Hanmi started a new Korean Phase 3 in April 2026 testing efpeglenatide added to metformin and dapagliflozin.
Can I buy efpeglenatide?
No. It is not approved anywhere. Efpeglenatide is a large conjugate of a peptide, a PEG linker and an antibody fragment, far harder to make than the short synthetic peptides sold online as research chemicals. Anything sold under its name or the HM11260C code outside Hanmi's trials or a future regulated Korean supply cannot be assumed to be the real molecule, and its purity and sterility are unknown.
Who Efpeglenatide Is NOT For
- •Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia: excluded from the Korean obesity Phase 3 and a boxed-warning contraindication for approved GLP-1 drugs.
- •History of acute or chronic pancreatitis: excluded from the Korean obesity Phase 3; efpeglenatide altered lipase and amylase levels in AMPLITUDE-O.
- •Clinically significant gastric emptying disorders, such as gastroparesis: excluded from the obesity trial; GLP-1 drugs slow gastric emptying.
- •Severe kidney disease (eGFR below 30): excluded from the obesity trial, although AMPLITUDE-O included people with eGFR of 25 to 59.9.
- •Pregnancy or breastfeeding: no human data, and weight-loss drugs are generally stopped in pregnancy.
- •Type 1 diabetes: not studied; the drug has been tested in type 2 diabetes and in obesity without diabetes.
Drug & Supplement Interactions
Efpeglenatide slows gastric emptying (6 mg weekly matched liraglutide 1.8 mg daily in a Phase 1b study), so it can change how quickly oral medicines are absorbed; drugs with a narrow therapeutic range need monitoring. With insulin or sulfonylureas, hypoglycemia risk rises: level 2 hypoglycemia occurred in up to 10% of participants across treatment groups (placebo included) in AMPLITUDE-L, on basal insulin, and in up to 4% in AMPLITUDE-S, on metformin with or without a sulfonylurea. SGLT2 inhibitors combine well: in AMPLITUDE-O, cardiovascular and kidney benefits and adverse events did not differ by baseline SGLT2 inhibitor use, and Hanmi's new diabetes Phase 3 adds efpeglenatide to metformin plus dapagliflozin. It should not be combined with other GLP-1 receptor agonists.
Safety Profile
Common Side Effects
Cautions
- • Investigational: not approved by the MFDS, FDA, EMA or any other regulator; Korean review pending
- • The Korean obesity Phase 3 excluded people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia, prior pancreatitis, clinically significant gastric emptying problems, and eGFR below 30
- • The cardiovascular benefit was shown in type 2 diabetes at 4 to 6 mg weekly; it has not been tested in obesity without diabetes or at the higher dose reported for the obesity trial
- • Full Korean Phase 3 results, including 64-week data and dropout rates, have not been published in a peer-reviewed journal
- • With insulin or sulfonylureas, hypoglycemia risk rises: in AMPLITUDE-L (on basal insulin), level 2 hypoglycemia occurred in up to 10% of participants across treatment groups, including placebo
What We Don't Know
Long-term safety in people with obesity but no diabetes, the efficacy and tolerability of the obesity dose in non-Korean populations, and whether the 64-week Korean data show continued loss or a plateau are all unpublished. Whether the Fc-conjugate design offers any real tolerability advantage over fatty-acid GLP-1 drugs has never been tested head-to-head.
Legal Status
United States
Not FDA-approved. No marketing application has been filed and no US trial is active; the US trials ran during the Sanofi era. It is not legally available through compounding pharmacies, telehealth or research-chemical suppliers.
International
South Korea: filed with the MFDS on 17 December 2025 under the GIFT fast-track program; under review as of early October 2026, with no approval announced. A Korean Phase 3 in type 2 diabetes is recruiting. Mexico: Laboratorios Sanfer holds exclusive distribution rights and is responsible for seeking Mexican approval. No application has been filed in Europe or elsewhere.
Sports & Competition
Not named on the WADA Prohibited List, but WADA's S0 category bans at all times any substance with no current approval from a government health authority for human therapeutic use, which covers efpeglenatide while it remains unapproved. If Korea approves it, S0 would no longer apply; approved GLP-1 drugs such as semaglutide and tirzepatide are not named on the Prohibited List and are not prohibited.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
Sanofi dropped efpeglenatide because it did not work.
Reality
Sanofi returned the rights in 2020 without citing a safety or efficacy problem. The investigators state that the AMPLITUDE trials were stopped for funding reasons, not safety or efficacy, and AMPLITUDE-O went on to show a 27% cut in major cardiovascular events.
Myth
Efpeglenatide is as effective as Wegovy for weight loss.
Reality
Its Korean Phase 3 showed 9.75% mean weight loss at 40 weeks. Semaglutide 2.4 mg produced 14.9% at 68 weeks in STEP 1. The trials are not directly comparable, but there is no evidence efpeglenatide matches semaglutide's weight loss.
Myth
Hanmi's trial showed up to 30% weight loss.
Reality
The up-to-30% figure describes the best individual results, not the typical one. The average was 9.75%, and 79.4% of participants lost at least 5%.
Myth
Efpeglenatide was approved in Korea in 2026.
Reality
As of early October 2026 the application is still under MFDS review. Korean press has speculated about timing, but no approval has been announced.
Published Research
13 studiesPotential Mediators of Efpeglenatide's Cardiovascular Benefit: An Exploratory Analysis of the AMPLITUDE-O Trial (Diabetes Obes Metab 2026)
Population pharmacokinetics of efpeglenatide in individuals with obesity and with type 2 diabetes (Front Pharmacol 2025)
Efficacy and safety of once-weekly efpeglenatide in people with suboptimally controlled type 2 diabetes: The AMPLITUDE-D, AMPLITUDE-L and AMPLITUDE-S randomized controlled trials (Diabetes Obes Metab 2023)
Exploring the Relationship Between Efpeglenatide Dose and Cardiovascular Outcomes in Type 2 Diabetes: Insights From the AMPLITUDE-O Trial (Circulation 2023)
Efficacy and Safety of Once-Weekly Efpeglenatide Monotherapy Versus Placebo in Type 2 Diabetes: The AMPLITUDE-M Randomized Controlled Trial (Diabetes Care 2022)
Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes (AMPLITUDE-O; N Engl J Med 2021)
The landmark trial: 4,076 people with type 2 diabetes and cardiovascular or kidney disease across 28 countries. Weekly efpeglenatide 4 or 6 mg reduced major adverse cardiovascular events (7.0% vs 9.2%; hazard ratio 0.73) and a kidney composite (hazard ratio 0.68) over a median 1.81 years.
Pharmacokinetic and dose-finding studies on efpeglenatide in patients with type 2 diabetes (Diabetes Obes Metab 2020)
Body weight management and safety with efpeglenatide in adults without diabetes: A phase II randomized study (Diabetes Obes Metab 2019)
The first obesity trial: 297 adults without diabetes on a hypocaloric diet, 20 weeks. Weekly and every-two-weeks efpeglenatide produced placebo-adjusted losses of 6.3 to 7.2 kg; 5% to 19% stopped because of adverse events.
Hanmi: Phase 3 trial confirms efficacy of GLP-1 drug efpeglenatide (Daily Pharm, October 2025)
Korean Phase 3 topline: 448 adults with obesity and no diabetes; -9.75% vs -0.95% weight change at week 40 (least-squares difference 8.13 points); 79.42% vs 14.49% lost at least 5%; nausea 16.72% vs 5.37%.
ClinicalTrials.gov NCT06174779 — Phase 3 of HM11260C in adults with obesity without diabetes
Hanmi files for approval of new GLP-1 weight-loss shot, tees up diabetes and DTx expansions (Korea Biomedical Review, December 2025)
Hanmi Pharm in spotlight as Korea's 1st obesity drug nears launch (The Korea Times, August 2026)
Sanofi decides to return rights for efpeglenatide to Hanmi (Korea Biomedical Review, September 2020)
Quick Facts
- Class
- GLP-1 Receptor Agonist
- Tier
- B
- Evidence
- Moderate
- Safety
- Moderate Data
- Updated
- Oct 2026
- Citations
- 13PubMed
Also known as
Tags
Peptide Families
Related Goals
Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.