What Is Efpeglenatide?

1. What is efpeglenatide and how does it work?

Efpeglenatide activates the GLP-1 receptor, the same target as semaglutide, liraglutide and dulaglutide. GLP-1 (glucagon-like peptide-1) is a gut hormone that boosts insulin release when blood sugar is high, lowers glucagon, slows stomach emptying, and reduces appetite. Drugs that mimic it lower blood sugar and body weight.

The active peptide is not human GLP-1. It is a modified version of exendin-4, the peptide first found in Gila monster venom and sold as exenatide. A 2025 population pharmacokinetic analysis describes efpeglenatide as “a CA-exendin-4 analogue covalently linked to the Fc fragment of human immunoglobulin G4 via a non-peptidyl linker,” the platform Hanmi calls LAPSCOVERY (Choi et al., Frontiers in Pharmacology 2025). The Fc fragment is the tail end of an antibody. The body recycles Fc-bearing proteins through a receptor called FcRn instead of breaking them down quickly, so the attached peptide stays in circulation far longer than exenatide’s few hours.

That same analysis pooled data from six clinical studies. It found a model-derived effective half-life of about 6–7 days, in line with clinically reported values of 5.6–7.5 days, which supports once-weekly dosing and predicts steady drug levels after about four weekly doses (Choi et al. 2025). Body weight and diabetes status shifted clearance somewhat, but the predicted differences in exposure were small enough that the authors did not recommend dose adjustments for those factors. Dulaglutide is the closest familiar comparison: it is also a GLP-1 agonist fused to an antibody Fc fragment, although the two are built differently.

Hanmi has used the same LAPSCOVERY approach for other long-acting peptides, including the GLP-1/glucagon agonist efinopegdutide, now licensed to Merck, and the triple agonist efocipegtrutide.

2. What did AMPLITUDE-O show about the heart and kidneys?

AMPLITUDE-O was the cardiovascular outcomes trial that Sanofi ran while it held the rights. It enrolled 4,076 people with type 2 diabetes at 344 sites in 28 countries. Everyone had either a history of cardiovascular disease or current kidney disease (an eGFR, the standard kidney-function estimate, of 25.0 to 59.9) plus at least one other cardiovascular risk factor. Participants were randomly assigned 1:1:1 to weekly efpeglenatide 4 mg, 6 mg, or placebo, and randomization was stratified by whether they took an SGLT2 inhibitor, a class of diabetes pills with its own heart and kidney benefits (Gerstein et al., NEJM 2021; NCT03496298).

The primary outcome was MACE (major adverse cardiovascular events): nonfatal heart attack, nonfatal stroke, or death from cardiovascular or undetermined causes.

Source: Gerstein et al., NEJM 2021. The kidney outcome combined a decline in kidney function with macroalbuminuria, meaning large amounts of protein in the urine.

The MACE result met both the noninferiority test (P less than 0.001) and the superiority test (P = 0.007). A hazard ratio of 0.73 means a 27% lower rate of events. Diarrhea, constipation, nausea, vomiting and bloating were more frequent with efpeglenatide than placebo, the usual GLP-1 pattern.

Two points make the trial notable. First, the four GLP-1 drugs previously shown to cut cardiovascular events were all structurally similar to human GLP-1; the NEJM authors framed AMPLITUDE-O as testing whether an exendin-based agonist would also help, and it did. Second, the trial deliberately included people with reduced kidney function and stratified by SGLT2 inhibitor use, groups that are common in real practice.

A 2026 post hoc analysis tried to explain the benefit. Efpeglenatide changed HbA1c, weight, pulse pressure, LDL cholesterol, urine albumin, eGFR, heart rate, and pancreatic enzymes. Together, changes in LDL cholesterol and urine albumin statistically accounted for about 29.6% of the reduction in MACE, while weight change did not (Raaschou-Oddershede et al., Diabetes Obes Metab 2026). That is an exploratory analysis, and most of the effect remained unexplained by the measured variables.

3. What did the diabetes and early obesity trials show?

Sanofi’s Phase 3 program was called AMPLITUDE. Besides the outcomes trial, the one fully published efficacy trial is AMPLITUDE-M, which tested efpeglenatide alone in 406 adults with type 2 diabetes not controlled by diet and exercise. Patients started at 2 mg weekly and stepped up by 2 mg every two weeks to their assigned 2, 4 or 6 mg dose (Frias et al., Diabetes Care 2022).

At week 30, HbA1c fell from a baseline of 8.1% to 6.9%, 6.6% and 6.4% on the three doses. Compared with placebo, the reductions were 0.5, 0.8 and 1.0 percentage points. Weight loss was modest at these doses: 2.3 kg more than placebo at 4 mg and 2.2 kg at 6 mg at week 30. Gastrointestinal events were the most common side effects, rose with dose, and were mostly mild to moderate; few patients had hypoglycemia (Frias et al. 2022). The paper notes that the study was initially sponsored by Sanofi, with sponsorship transferred to Hanmi after the final database lock.

The first obesity data came earlier, from a 20-week Phase 2 trial in 297 adults without diabetes, with a BMI of at least 30 or at least 27 with a weight-related condition. Participants received 4 mg weekly, 6 mg weekly, 6 mg every two weeks, 8 mg every two weeks, or placebo, all with a reduced-calorie diet. Placebo-adjusted weight loss ranged from 6.3 kg to 7.2 kg, with the largest effect on 6 mg weekly (Pratley et al., Diabetes Obes Metab 2019). At week 21, 45.8% to 53.4% of treated participants had lost at least 5% of body weight, against 3.3% on placebo. Gastrointestinal adverse events affected 64.4% to 83.1% of treated groups versus 46.7% on placebo, and discontinuation because of side effects ranged from 5% to 19% across arms. Most nausea and vomiting occurred within the first few injections and faded over time.

The doses in these early trials were capped at 6–8 mg. The Korean obesity program later went higher, to a 10 mg maintenance dose.

4. Why did Sanofi return efpeglenatide?

In November 2015, Hanmi licensed three diabetes candidates to Sanofi: efpeglenatide, a weekly insulin, and a weekly GLP-1/insulin combination. The deal was worth up to 3.9 billion euros including milestones, with 400 million euros upfront. Sanofi handed back two of the three in 2016, and Hanmi repaid 196 million euros of the upfront payment for those (Korea JoongAng Daily, September 2020).

Efpeglenatide stayed with Sanofi until 2020. Sanofi gave notice in May 2020 that it wanted out, and after a 120-day negotiation it finalized the return in September 2020 and notified the trial sites. It had been running five trials. Hanmi took over the one nearing completion and the other four were halted (Korea JoongAng Daily, September 2020). Sanofi’s new leadership had moved the company away from diabetes and cardiovascular research. The exit was a portfolio decision, not a safety finding, and it is the reason a drug with a positive cardiovascular outcomes trial never reached Western markets.

The AMPLITUDE-O paper, published in June 2021, still lists Sanofi as the funder (Gerstein et al. 2021). By then no large company was planning to file it for diabetes, and Hanmi turned to obesity, a larger market in Korea where it could run trials and manufacture the drug itself (Seoul Economic Daily, October 2026).

5. What did the Korean Phase 3 obesity trial show?

Hanmi’s Korean Phase 3 trial, registered as NCT06174779, was a randomized, double-blind, placebo-controlled study in adults with obesity and no diabetes. Korea’s drug regulator, the Ministry of Food and Drug Safety (MFDS), cleared it on October 23, 2023. It randomized 448 people, 299 to efpeglenatide and 149 to placebo. The two primary outcomes were the percentage change in body weight and the share losing at least 5% of body weight at week 40. A 24-week extension then continued to week 64 (Hanmi disclosure summary, October 2025). The registry lists the trial as completed: it started January 3, 2024, reached primary completion on August 14, 2025, and finished on March 13, 2026 (NCT06174779).

Participants were younger and lighter than in most Western obesity trials: average age 43, average weight 89 kg, and average BMI about 32 (Korea JoongAng Daily, October 2026). The dose started at 2 mg and rose through 4, 6 and 8 mg over 12 weeks to a 10 mg weekly maintenance dose.

In Hanmi’s October 27, 2025 regulatory disclosure, both primary endpoints were met (Hanmi disclosure summary):

The 10% and 15% responder figures come from Korea Biomedical Review’s report on the approval (Korea Biomedical Review, October 2026).

Coverage of the approval gave slightly different numbers: 9.02% weight loss versus 0.89% on placebo, and 75.1% versus 13.5% losing at least 5%, with diarrhea at 17.6%, nausea 16.6%, indigestion 15.6%, constipation 14.6% and vomiting 11.6% (Korea JoongAng Daily, October 2026). The likely explanation is a different analysis population or statistical method, but the sources do not say which, so both sets are shown here. Either way, the placebo-adjusted effect is roughly 8 percentage points at 40 weeks. Hanmi has said weight loss tended to hold through week 64, but it has not published the week-64 average.

6. When and how was efpeglenatide approved in Korea?

The timeline moved quickly once the topline data were in:

Sources: Korea Biomedical Review, December 2025; Hanmi and Sanfer release, January 2026; Seoul Economic Daily; BizWatch, October 29, 2026.

The approved indication is chronic weight management, alongside a reduced-calorie diet and exercise, in adults without diabetes who have a BMI of 30 or more, or a BMI of 27 to under 30 with at least one weight-related condition such as high blood pressure, abnormal blood lipids, sleep apnea or cardiovascular disease (Korea JoongAng Daily, October 2026). The auto-injector was approved in 2, 4, 6, 8 and 10 mg strengths (Seoul Economic Daily).

Korean reports put the supply price for the first four weeks at about 130,000 won. That is a supply price, not what a patient pays, and it was reported as lower than the low-dose supply prices of Wegovy and Mounjaro in Korea (Korea Biomedical Review). Hanmi makes both the active ingredient and the finished product at its Pyeongtaek plant, which it pitches as protection against the supply shortages seen with imported drugs.

On launch day, BizWatch found that most Seoul clinics it surveyed had not yet received stock and expected prescribing to begin the following day (BizWatch, October 29, 2026). This page was checked on November 8, 2026.

7. What is next for efpeglenatide outside obesity and outside Korea?

Hanmi is running a Phase 3 trial of efpeglenatide combined with an SGLT2 inhibitor and metformin in type 2 diabetes, with a diabetes indication targeted for 2028 (Hanmi and Sanfer release). In December 2025 Hanmi also described plans for prefilled-syringe and multi-dose pen versions, and for pairing the drug with a digital health device (Korea Biomedical Review, December 2025).

The first export deal is with Laboratorios Sanfer in Mexico, signed in January 2026. Hanmi supplies the product, and Sanfer is responsible for Mexican regulatory approval, marketing and sales. The release did not give a Mexican approval date (PR Newswire, January 2026).

No FDA or EMA filing has been announced. The obesity approval rests on a Korean-only trial, and US or European regulators would normally expect larger, longer trials in their own populations before approving it for weight management.

8. How does efpeglenatide compare with other GLP-1 drugs?

There is no head-to-head trial with semaglutide or tirzepatide. Korean press coverage noted that the 9–10% average loss at 40 weeks is below the roughly 15–20% averages reported in the longer Wegovy and Mounjaro trials, while cautioning that trial length and population differ (Korea Biomedical Review). The Korean trial’s participants started at a lower BMI, around 32 versus about 38 in the imported drugs’ trials according to its principal investigator, and the primary result was measured at 40 weeks rather than 68–72. Hanmi’s pitch rests more on price, supply and gastrointestinal tolerability than on maximum weight loss, and the tolerability claim has not been tested head to head.

9. What does efpeglenatide mean for people on GLP-1 therapy?

It is a GLP-1 drug, not an add-on. Efpeglenatide acts on the same receptor as semaglutide, liraglutide and dulaglutide. Taking it alongside another GLP-1 agonist would double up on one mechanism, and no trial has tested that combination.

The side effects are the familiar ones. Nausea, vomiting, diarrhea, constipation and indigestion led the list in every trial. In the Phase 2 obesity trial, most nausea came in the first few injections, which is why every program used gradual dose escalation (Pratley et al. 2019). The dose titration guide explains why stepping up slowly matters.

Muscle and nutrition still matter. None of the published efpeglenatide trials reported detailed body-composition results, so how much of the lost weight was lean mass is not established. The general evidence on GLP-1 drugs and muscle loss applies: adequate protein and resistance training are the main tools to protect muscle during weight loss.

Its long half-life affects stopping and switching. With an effective half-life of about a week, efpeglenatide takes several weeks to clear after the last dose. The guide to how long a GLP-1 stays in your system explains the general arithmetic, and a half-life chart can show how drug levels fall after a dose.

The heart data are for diabetes. AMPLITUDE-O enrolled only people with type 2 diabetes and existing heart or kidney disease. Whether efpeglenatide reduces cardiovascular events in people with obesity but no diabetes has not been tested.

10. Efpeglenatide FAQ

• Is efpeglenatide approved?

  Yes, in South Korea only. The Ministry of Food and Drug Safety approved it on October 7, 2026 as Eppe Auto Injector for chronic weight management, alongside diet and exercise, in adults with obesity or overweight who do not have diabetes. It is not approved in the United States or the European Union as of November 2026, and no US or EU filing has been announced.

• How much weight loss does efpeglenatide cause?

  In Hanmi's Korean Phase 3 trial, mean weight loss at 40 weeks was 9.75% versus 0.95% on placebo in the company's October 2025 disclosure, a placebo-adjusted difference of 8.13 points. Coverage of the approval reported 9.02% versus 0.89%, apparently from a different analysis. About half of treated participants lost at least 10%. Results at 64 weeks have not been published.

• Is efpeglenatide the same as exenatide?

  No, but they are related. Efpeglenatide is built on a modified exendin-4, the same lizard-derived peptide family as exenatide (Byetta, Bydureon). Hanmi attached it to a human antibody Fc fragment so that it lasts about a week instead of hours. It is a separate drug with its own trials.

• Why did Sanofi give efpeglenatide back?

  Sanofi notified Hanmi in May 2020 that it would return all rights and finalized the exit in September 2020. Sanofi's leadership at the time cited a change in strategy away from diabetes and cardiovascular research, not a safety signal. The AMPLITUDE-O cardiovascular trial still completed and was published in 2021, with positive results.

• Does efpeglenatide protect the heart?

  In people with type 2 diabetes, AMPLITUDE-O showed a 27% lower risk of heart attack, stroke, or cardiovascular death versus placebo, and fewer kidney outcome events. That trial did not include people with obesity but no diabetes, so the Korean obesity approval does not carry a heart-protection claim based on it.

• What are the side effects of efpeglenatide?

  Mainly gastrointestinal, as with other GLP-1 drugs. In the Korean obesity trial, Hanmi reported nausea in 16.72%, vomiting in 11.71%, and diarrhea in 17.73% of treated participants versus 5.37%, 2.01%, and 4.70% on placebo. Approval coverage also listed indigestion and constipation at roughly 15%.

• Can I get efpeglenatide outside Korea?

  Not as an approved medicine. Hanmi signed a distribution deal for Mexico with Laboratorios Sanfer in January 2026, but Sanfer still has to win Mexican approval. Products sold online as efpeglenatide outside these channels are not the regulated drug.

• Is efpeglenatide better than Wegovy or Mounjaro?

  There is no head-to-head trial. Its average weight loss in the Korean trial was lower than published figures for semaglutide 2.4 mg or tirzepatide, but its trial was shorter (40 weeks at the primary analysis) and enrolled people with a lower average BMI. Hanmi is competing mainly on price and domestic supply in Korea.

11. Sources