Efpeglenatide

Origin and structure

Efpeglenatide was developed by Hanmi Pharmaceutical in Seoul, first under the names LAPS-Exendin and HM11260C. Its active part is a modified form of exendin-4, a 39-amino-acid peptide isolated in 1992 from the venom of the Gila monster (Heloderma suspectum). Exendin-4 activates the human GLP-1 receptor, and made synthetically it is the drug exenatide. In efpeglenatide one of its amino acids is altered, giving what Hanmi calls CA-exendin-4.

Hanmi's Lapscovery platform (Long Acting Protein/Peptide Discovery) then joins this peptide, through a short polyethylene glycol (PEG) linker that is not made of amino acids, to the Fc fragment of a human IgG4 antibody, which Hanmi produces in E. coli bacteria. The peptide is only a small part of the result: according to the Korean product information, a 10 mg dose contains 0.77 mg of CA-exendin-4. The carrier makes the body clear the drug far more slowly. In people with type 2 diabetes the half-life was 135 to 180 hours, about 5.6 to 7.5 days, and with weekly injections blood levels varied little between doses.

In November 2015 Hanmi licensed the worldwide rights to Sanofi, together with a weekly insulin and a weekly combination of the two, a package the companies called the Quantum Project. Sanofi gave it the code SAR439977 and ran a phase 3 programme in type 2 diabetes. In December 2019 Sanofi announced that it was ending its research in diabetes and cardiovascular disease and would not launch efpeglenatide, while completing the ongoing studies and looking for a partner. In May 2020 it told Hanmi that it would return all rights. Hanmi took the compound back and developed it further for obesity in Korea.

How it works

Efpeglenatide activates the GLP-1 receptor, the same target as semaglutide, liraglutide and dulaglutide. In the pancreas this raises insulin release and lowers glucagon when blood glucose is high. It also slows the emptying of the stomach and reduces appetite, so people eat less.

In phase 2 Hanmi also tried injections every two weeks and once a month. Monthly doses lowered HbA1c, but blood levels swung much more between injections (peak-to-trough ratios of 5.9 to 12.9, against 1.3 to 1.4 with weekly doses). The phase 3 trials and the Korean label use one injection a week.

The Korean product information adds two points about exposure: people with obesity but without diabetes had higher blood levels than people with type 2 diabetes, and lighter people had higher levels than heavier ones. The approved obesity dose goes up to 10 mg a week, while the diabetes trials stopped at 6 mg.

Is efpeglenatide approved?

Only in South Korea. The Ministry of Food and Drug Safety (MFDS) approved it on 7 October 2026 under the brand name Eppe, a prefilled auto-injector in strengths of 2, 4, 6, 8 and 10 mg, as a prescription medicine for weight management in adults without diabetes. Korea counts it as its 45th domestically developed new drug, and Korean doctors can prescribe it from 29 October 2026.

In the EU and the US it has no marketing authorisation. No efpeglenatide medicine is listed by the EMA or in the FDA's approval records, so none is registered in the Netherlands, and no filing with either agency has been announced.

Efpeglenatide is also unlike most peptides offered for research. By weight, more than nine-tenths of each dose is the PEG linker and the antibody fragment, not a short synthetic chain. Anything sold under the name outside the Korean prescription channel is not Eppe, has no marketing authorisation and may not be used in people.

• South Korea, weight management: approved 7 October 2026 for long-term weight management alongside a reduced-calorie diet and exercise in adults without diabetes with a BMI of 30 or more, or 27 to under 30 with at least one weight-related condition such as high blood pressure, abnormal blood lipids, sleep apnoea or cardiovascular disease. Hanmi filed on 17 December 2025, and the MFDS reviewed it in its GIFT fast-track programme.
• South Korea, type 2 diabetes: Hanmi started a Korean phase 3 trial in April 2026 (NCT07379333; 118 adults planned, on metformin and dapagliflozin, HbA1c after 36 weeks) and plans to add a diabetes indication in 2028.
• Mexico: in January 2026 Hanmi signed an exclusive deal with Laboratorios Sanfer, which is responsible for approval, marketing and sales there.
• EU and US: not authorised. Sanofi's phase 3 trials included sites in the US, Canada and several EU countries, but Sanofi dropped the planned launch in December 2019.

What the research shows

The evidence comes in two parts. Sanofi's AMPLITUDE programme tested efpeglenatide in type 2 diabetes in five randomised phase 3 trials with more than 6,000 participants; four of them, AMPLITUDE-O included, were ended early by the sponsor for funding reasons, not because of safety or efficacy concerns. Hanmi then tested a higher dose for obesity in one Korean trial, whose results so far appear in the Korean product information but not in a peer-reviewed journal. The headline results:

• Phase 2, obesity without diabetes (Diabetes Obes Metab 2019): 297 adults on a reduced-calorie diet; after 20 weeks, weight fell 6.3 to 7.2 kg more than on placebo across four schedules (4 or 6 mg weekly, 6 or 8 mg every two weeks). Between 5% and 19% stopped because of side effects.
• AMPLITUDE-M (Diabetes Care 2022): 406 adults with type 2 diabetes on diet and exercise alone; at week 30, HbA1c fell from 8.1% to 6.9%, 6.6% and 6.4% on 2, 4 and 6 mg, or 0.5, 0.8 and 1.0 percentage points more than on placebo.
• AMPLITUDE-D, -L and -S (Diabetes Obes Metab 2023): in 908 people on metformin, 4 and 6 mg lowered HbA1c as much as dulaglutide 1.5 mg after 56 weeks, with about 3 kg of weight loss in every group. In the placebo-controlled AMPLITUDE-L (on basal insulin) and AMPLITUDE-S (on metformin with or without a sulfonylurea), HbA1c and weight fell numerically more on efpeglenatide.
• AMPLITUDE-O (NEJM 2021): 4,076 people with type 2 diabetes and either cardiovascular disease (89.5%) or kidney disease plus another risk factor, at 344 sites in 28 countries, followed for a median of 1.8 years; the trial ended with 314 primary events instead of the planned 330 because of Sanofi's funding decision. A heart attack, stroke or cardiovascular death occurred in 7.0% on 4 or 6 mg against 9.2% on placebo (hazard ratio 0.73, 95% CI 0.58 to 0.92), and a composite kidney outcome in 13.0% against 18.4% (hazard ratio 0.68, 95% CI 0.57 to 0.79). Hospitalisation for heart failure was also less frequent (1.5% against 2.3%, hazard ratio 0.61), while the difference in death from any cause (4.1% against 5.1%) was not statistically significant. Over the follow-up, HbA1c averaged 1.24 percentage points and weight 2.6 kg lower than on placebo.
• Follow-up analyses of AMPLITUDE-O: the benefit rose with the dose (hazard ratio 0.65 on 6 mg and 0.82 on 4 mg, the latter not statistically significant), and it was much the same with or without an SGLT2 inhibitor, which about 15% of participants were taking at the start.
• Korean phase 3 in obesity (NCT06174779): 448 Korean adults without diabetes, mean age 43 and mean BMI 32, randomised 2:1 to efpeglenatide escalated to 10 mg or placebo. After 40 weeks weight fell 9.02% against 0.89% (difference 8.1 percentage points, 95% CI 6.8 to 9.4), and 75.1% against 13.5% lost at least 5%. In a 24-week open-label extension in which everyone received efpeglenatide, the label reports that the weight loss was broadly maintained up to week 64.

Side effects and warnings

As with other GLP-1 drugs, most side effects are gastrointestinal. In the 40-week placebo-controlled part of the Korean obesity trial, people on efpeglenatide reported diarrhoea (17.6% against 4.8% on placebo), nausea (16.6% against 5.4%), indigestion (15.6% against 4.8%), constipation (14.6% against 2.0%), injection-site reactions (13.6% against 8.8%) and vomiting (11.6% against 2.0%). They were mostly mild to moderate and more frequent while the dose was being raised, and over the full 64 weeks 1.2% stopped for good because of gastrointestinal side effects. In the diabetes trial AMPLITUDE-M, 8.8% to 17.2% stopped because of side effects, against 4.9% on placebo, more often at higher doses.

The Korean product information also reports a resting heart rate on average 6.8 beats per minute higher (placebo 0.1 lower), with 8.4% of participants at some point above 100 beats per minute and at least 15 above their starting rate, against 0.7% on placebo. Gallstones occurred in 1.3% against none on placebo, and over 64 weeks two of 434 treated participants had gallstones that led to inflammation of the gallbladder and bile ducts, and both had their gallbladder removed. The pancreatic enzymes amylase and lipase rose by 16.0% and 49.8% on average, low blood sugar was reported by 1.3% against none on placebo, and 17.5% developed antibodies against the drug (3% neutralising); those with antibodies had more injection-site and allergic reactions, with no sign that the drug worked less well.

Efpeglenatide caused thyroid C-cell tumours in rats and mice. The Korean label carries this as a warning and rules out people with a personal or family history of medullary thyroid carcinoma or MEN 2. It also warns about pancreatitis, gallbladder disease, dehydration leading to kidney injury, inhaling stomach contents under anaesthesia, serious allergic reactions, and depression or suicidal thoughts. It is not for use in pregnancy or breastfeeding, and according to the label treatment should stop at least nine weeks before a planned pregnancy. It has not been studied for weight management in people with diabetes, moderate or severe kidney disease, liver disease or a history of serious mental illness, and the obesity data come from a single 64-week trial in Korean adults.

Efpeglenatide versus dulaglutide and semaglutide

Dulaglutide (Trulicity) uses a similar idea: it too is a GLP-1 receptor agonist attached to the Fc part of a human IgG4 antibody. The differences are in the details. Dulaglutide carries a GLP-1 analogue joined to the Fc part by a short peptide and is made as a single fusion protein in hamster cells, while efpeglenatide carries an exendin-4 analogue joined by a PEG linker, with the carrier made in bacteria. In AMPLITUDE-D, the only trial that compared the two directly, efpeglenatide 4 and 6 mg lowered HbA1c as much as dulaglutide 1.5 mg over 56 weeks, with similar weight loss.

Efpeglenatide has never been compared directly with semaglutide. In the Korean trial it gave 9.0% weight loss after 40 weeks, while semaglutide 2.4 mg gave 14.9% after 68 weeks in STEP 1; the trials differ in length, population (a mean BMI of 32 in Korea) and analysis, so the figures cannot simply be set side by side. Semaglutide and dulaglutide are approved in the EU and the US and have their own cardiovascular outcome trials (SUSTAIN 6 and SELECT for semaglutide, REWIND for dulaglutide). Efpeglenatide has a positive outcome trial as well, but it is approved only in South Korea, only for weight management and at a higher dose (10 mg) than the 4 and 6 mg tested in AMPLITUDE-O.

Frequently asked questions

Is efpeglenatide approved?

Only in South Korea, where the MFDS approved it on 7 October 2026 under the brand name Eppe, for weight management in adults without diabetes. It has no approval from the EMA or the FDA, and no filing with either agency has been announced. Sanofi tested it for type 2 diabetes but dropped its launch plans in December 2019.

Why did Sanofi give efpeglenatide back to Hanmi?

For business reasons. In December 2019 Sanofi's new strategy ended its research in diabetes and cardiovascular disease and dropped the planned launch of efpeglenatide, and in May 2020 it told Hanmi it would return all rights. That decision came before the AMPLITUDE-O results were published in 2021, and according to Hanmi, Sanofi said the decision had nothing to do with the drug's efficacy or safety.

Is efpeglenatide available in the Netherlands?

No. There is no EU authorisation, so there is no registered product that a Dutch doctor could prescribe or a pharmacy could dispense. The only approved product, Eppe, is a Korean prescription medicine. Material sold online under the name is not a medicine and may not be used in people.

How much weight do people lose on efpeglenatide?

In the Korean phase 3 trial, adults without diabetes and with a mean BMI of 32 lost 9.0% of their body weight after 40 weeks on doses built up to 10 mg, against 0.9% on placebo, and 75% lost at least 5%. In the 2019 phase 2 trial, weight fell 6.3 to 7.2 kg more than on placebo after 20 weeks. At the lower doses used in type 2 diabetes the effect was smaller: 2.6 kg more than placebo in AMPLITUDE-O.

What is the difference between efpeglenatide and exenatide?

Both are based on exendin-4, a peptide from the venom of the Gila monster. Exenatide is synthetic exendin-4 on its own, which the body clears within hours unless it is packed into a slow-release formulation. Efpeglenatide is a slightly modified exendin-4 chemically attached to an antibody fragment, which stretches its half-life to about a week.

Is efpeglenatide banned in sport?

It is not named on the WADA Prohibited List, and GLP-1 drugs are not prohibited. The catch-all class S0 bans substances that no government health authority has approved for human use, which covered efpeglenatide until South Korea approved it on 7 October 2026; since then S0 no longer applies. In the Netherlands the Dopingautoriteit applies the same list.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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