Peptide education
Efpeglenatide
HM11260C · HM-11260C · Eppe
Efpeglenatide is a long-acting GLP-1 receptor agonist. South Korea approved it as Eppe for chronic weight management in certain adults without diabetes, alongside a reduced-calorie diet and exercise. Separate trials have studied it in people with type 2 diabetes.
In a Korean obesity trial, efpeglenatide produced more weight loss than placebo at 40 weeks. A separate diabetes trial found fewer major cardiovascular events. Approval and available products depend on jurisdiction.
Overview
Quick answer
The Korean weight-management approval and the AMPLITUDE-O cardiovascular trial answer different questions. The Korean label covers specified adults without diabetes. AMPLITUDE-O studied adults with type 2 diabetes and elevated cardiovascular risk.
Who is covered by the South Korean approval?
The label covers adults without diabetes who have a starting BMI of at least 30, or a BMI of at least 27 but below 30 with a weight-related condition such as hypertension, dyslipidemia, sleep apnea, or cardiovascular disease. It is used alongside a reduced-calorie diet and exercise.
What did the Korean weight-management trial find?
The trial randomized 448 Korean adults without diabetes. In the full analysis set of 298 on efpeglenatide and 148 on placebo, adjusted mean weight changes at week 40 were minus 9.02% and minus 0.89%, respectively. The difference was 8.13 percentage points in favor of efpeglenatide.
What did the cardiovascular trial find?
In AMPLITUDE-O, 7.0% of participants assigned efpeglenatide and 9.2% assigned placebo had a first major cardiovascular event over a median follow-up of 1.81 years. Participants had type 2 diabetes and prior cardiovascular disease or kidney disease with another cardiovascular risk factor.
Is it approved in the United States or the European Union?
The Drugs@FDA active-ingredient search returned no approved product, and the EMA medicines table had no matching centralized authorization. EMA's table does not cover every national authorization.
What side effects and warnings matter?
The Korean label reports gastrointestinal effects and injection-site reactions. It also warns about thyroid C-cell tumors seen in rodents, whose relevance to humans is uncertain, and lists specific thyroid cancer and MEN2 contraindications.
Evidence
Evidence snapshot
The Korean indication is for adults meeting the label's BMI and weight-related condition criteria, alongside diet and exercise.
At week 40, adjusted mean weight change was minus 9.02% with efpeglenatide versus minus 0.89% with placebo. Participants were Korean adults without diabetes.
In high-risk adults with type 2 diabetes, the first major cardiovascular event occurred in 7.0% assigned efpeglenatide and 9.2% assigned placebo; the hazard ratio was 0.73.
In the Korean label's 40-week comparison, diarrhea occurred in 17.6% receiving efpeglenatide versus 4.8% receiving placebo; nausea occurred in 16.6% versus 5.4%.
No matching FDA-approved product or centralized EMA authorization was found in the named databases. National authorizations outside those searches need separate verification.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| Efpeglenatide is investigational everywhere. | The South Korean regulator approved Eppe for chronic weight management in specified adults without diabetes. | Incorrect. The Korean authorization is real and limited to its label. Approval status differs across jurisdictions. |
| The cardiovascular trial proves the Korean obesity indication treats diabetes. | AMPLITUDE-O studied people with type 2 diabetes and elevated cardiovascular risk. The Korean weight-management label specifies patients without diabetes. | The trial and label describe different populations and outcomes. The cardiovascular result does not add a diabetes indication to that label. |
| The Korean trial compared efpeglenatide with placebo for 64 weeks. | Its placebo-controlled period was 40 weeks. During the following 24-week open-label extension, participants received efpeglenatide. | The 64-week study duration included an extension without a concurrent placebo group. |
Bottom line
Main takeaway
Eppe has a specific South Korean obesity approval. Its approval in one country does not make an identically named product approved elsewhere.
The Korean weight trial excluded diabetes, while AMPLITUDE-O enrolled adults with type 2 diabetes and cardiovascular or kidney risk.
The Korean label reports adjusted weight change at week 40. AMPLITUDE-O measured a composite of nonfatal heart attack, nonfatal stroke, and cardiovascular or undetermined death.
Identity
What it is
Efpeglenatide is an exendin-based GLP-1 receptor agonist designed for longer activity. Its clinical programs have evaluated weight, glucose control, and cardiovascular outcomes in different groups of adults.
South Korea's Eppe label addresses weight management without diabetes. The manufacturer also reported starting a separate phase 3 diabetes study in people taking metformin and dapagliflozin.
Use context
Routes, doses, and cycle patterns
The Korean product label and the diabetes trial used different target doses in different populations. Both describe once-weekly subcutaneous administration.
Human studies and product labels
South Korean Eppe label and obesity trial
- Purpose
- Chronic weight management in qualifying adults without diabetes
- Context
- Korean product information and phase 3 trial
- Route
- Subcutaneous
- Amount
- 2 mg starting dose, increased through 4, 6, and 8 mg to 10 mg maintenance
- Frequency
- Once weekly
- Duration
- 40-week placebo-controlled trial followed by a 24-week open-label extension
The label describes 2 mg for two weeks, 4 mg for two weeks, 6 mg for four weeks, and 8 mg for four weeks before 10 mg maintenance. It allows changes when tolerability is inadequate. The trial and approved indication exclude diabetes.
AMPLITUDE-O cardiovascular trial
- Purpose
- Cardiovascular outcomes in adults with type 2 diabetes and elevated risk
- Context
- Randomized, placebo-controlled phase 3 study
- Route
- Subcutaneous
- Amount
- 4 or 6 mg maintenance after a 2 mg starting dose
- Frequency
- Once weekly
- Duration
- Median follow-up of 1.81 years
The 4 mg arm started at 2 mg for four weeks. The 6 mg arm continued at 4 mg for four additional weeks before reaching 6 mg. The registry reports early termination by sponsor decision, unrelated to safety.
AMPLITUDE-M glycemic trial
- Purpose
- Glycemic control in type 2 diabetes
- Context
- Randomized phase 3 study in adults inadequately controlled with diet and exercise alone
- Route
- Subcutaneous
- Amount
- 2, 4, or 6 mg study groups
- Frequency
- Once weekly
- Duration
- Up to 56 weeks; primary HbA1c assessment at week 30
The study evaluated glucose control and weight in a different population from the Korean obesity trial.
What varies
- Jurisdiction: the Korean indication is specific to adults without diabetes.
- Endpoint: weight change and major cardiovascular events were measured in different trials.
- Safety: the Korean label includes contraindications and warnings beyond gastrointestinal effects.
Research
Research evidence
The South Korean label describes a placebo-controlled obesity trial in 448 Korean adults without diabetes. AMPLITUDE-O enrolled 4,076 adults with type 2 diabetes and elevated cardiovascular risk, while AMPLITUDE-M assessed glycemic control in a different diabetes population. The studies should be interpreted by their populations and endpoints.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Korean phase 3 obesity trial, NCT06174779 | 448 Korean adults with obesity or qualifying overweight without diabetes | Randomized, double-blind, placebo-controlled trial | Once-weekly efpeglenatide escalated to 10 mg, or placebo | Among 298 efpeglenatide and 148 placebo participants in the full analysis set, adjusted mean weight change at week 40 was minus 9.02% versus minus 0.89%. The adjusted difference was minus 8.13 percentage points. | The full analysis set included treated participants with at least one post-baseline weight assessment through week 40; missing data were imputed. The 40-week placebo-controlled period was followed by a 24-week open-label extension. The trial enrolled Korean adults without diabetes. | Controlled phase 3 trial reported in the Korean label |
| AMPLITUDE-O, NCT03496298 | 4,076 adults with type 2 diabetes and prior cardiovascular disease or kidney disease plus another cardiovascular risk factor | Randomized, placebo-controlled phase 3 outcomes trial | Efpeglenatide 4 or 6 mg weekly, pooled for the main comparison | A first major cardiovascular event occurred in 7.0% of the pooled active groups versus 9.2% on placebo over median follow-up of 1.81 years, hazard ratio 0.73. The kidney composite included new macroalbuminuria as well as measures of reduced kidney function. | The sponsor ended the trial early for reasons reported as unrelated to safety. Results apply to the enrolled high-risk diabetes population. | Controlled phase 3 outcomes trial |
| AMPLITUDE-M, NCT03353350 | Adults with type 2 diabetes inadequately controlled with diet and exercise alone | Randomized, double-blind, placebo-controlled phase 3 trial | Once-weekly efpeglenatide 2, 4, or 6 mg versus placebo | Each active group had a greater reduction in HbA1c than placebo at week 30. The 4 and 6 mg groups also had greater weight reductions. | This glycemic-control study differs from the Korean obesity trial and does not itself establish a diabetes approval. | Controlled phase 3 glycemic trial |
Use context
Reported use context
The Korean label and the clinical trials describe weekly subcutaneous dosing, with different maintenance amounts and populations.
Study and label context
Escalation from 2 mg to 10 mg weekly; placebo comparison through week 40.
Study-reported schedule in adults without diabetes.Escalation from 2 mg to maintenance of 4 or 6 mg weekly, compared with placebo.
Study-reported schedule in adults with type 2 diabetes and elevated cardiovascular risk.Cautions
Safety and unknowns
- During the Korean trial's placebo-controlled period, diarrhea was reported in 17.6% of the efpeglenatide group and 4.8% of the placebo group; nausea in 16.6% and 5.4%; and vomiting in 11.6% and 2.0%. Injection-site reactions were also reported.
- The Korean label describes thyroid C-cell tumors in rodent studies. It says the relevance to humans is uncertain and contraindicates the drug for people with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia type 2.
- The label also addresses pancreatitis, gallbladder disease, severe gastrointestinal illness, dehydration and kidney injury, and aspiration during anesthesia or deep sedation. Its restrictions for pregnancy, breastfeeding, and other populations are relevant to clinical decisions.
- In AMPLITUDE-O, diarrhea, constipation, nausea, vomiting, or bloating occurred more often with efpeglenatide than placebo. That safety report comes from adults with type 2 diabetes and elevated cardiovascular risk.
Product quality
Product identity and quality
The South Korean approval applies to a specified product and indication. Another product using the ingredient name has its own identity, manufacturing, and legal-status questions.
Product and jurisdiction
A regional authorization does not establish approval for a product in another country.
Identity and handling
The ingredient name alone does not verify concentration, sterility, formulation, or storage conditions.
Mechanism
How it is proposed to work
Efpeglenatide activates the GLP-1 receptor. This pathway helps regulate appetite and blood glucose and can slow the passage of food from the stomach.
Its long-acting exendin-based design supports weekly dosing in the studied formulations. Effects on weight and cardiovascular events were evaluated in separate clinical trials.
FAQ
Common questions
Is efpeglenatide approved?
South Korea approved Eppe for specified chronic weight management in adults without diabetes. No FDA-approved product was found in the ingredient search.
Does the Korean approval cover type 2 diabetes or cardiovascular prevention?
The Korean label reviewed here is for specified weight management in adults without diabetes. The diabetes cardiovascular trial is separate from that indication.
Details
Technical details
Sources
References
- 1.
South Korea Ministry of Food and Drug Safety. Eppe auto-injector product information
Korean-language approved product information, including indication, study outcomes, dosing, and warnings.
- 2.
ClinicalTrials.gov. HM11260C phase 3 trial in adults without diabetes
NCT06174779
Completed Korean obesity trial registered under the development code HM11260C.
- 3.
PubMed. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes
doi:10.1056/NEJMoa2108269 PMID:34215025 NCT03496298
Randomized cardiovascular outcomes trial in adults with type 2 diabetes and elevated cardiovascular risk.
- 4.
ClinicalTrials.gov. AMPLITUDE-O trial registry and results
NCT03496298
Lists the study arms, escalation, and early termination by sponsor decision, reported as unrelated to safety.
- 5.
PubMed. AMPLITUDE-M randomized trial of efpeglenatide in type 2 diabetes
doi:10.2337/dc21-2656 PMID:35671039 NCT03353350
Phase 3 glycemic-control trial in adults inadequately controlled with diet and exercise alone.
- 6.
Hanmi Pharmaceutical. Hanmi report on Korean phase 3 diabetes trial initiation
Sponsor reports initiation of a separate phase 3 trial; it does not report completed outcomes.
- 7.
FDA. Drugs@FDA active ingredient search for efpeglenatide
The openFDA Drugs@FDA ingredient search returned no match. The linked FDA search can be used to recheck; database coverage has limits.
- 8.
European Medicines Agency. EMA medicines data table
No efpeglenatide match in the downloaded EMA table; it does not establish every national authorization.