What Is Efinopegdutide?

1. How does efinopegdutide work?

GLP-1 receptor agonism supplies the appetite and glucose effects of semaglutide. Glucagon receptor agonism adds a liver action: glucagon receptors are concentrated in hepatocytes, where activation increases fat oxidation and energy expenditure and reduces liver fat directly. That is why every GLP-1/glucagon dual agonist in development, pemvidutide, survodutide, and efinopegdutide, has a liver disease as a lead or major indication. The what is glucagon page covers the hormone, and the what is MASH page the disease.

Efinopegdutide itself has moved through five registered efinopegdutide- or JNJ-64565111-labeled human trials on ClinicalTrials.gov: a Phase 1 single- and multiple-ascending-dose study, the Phase 2a head-to-head against semaglutide, a Phase 2a dosing-regimen study comparing weekly and biweekly schedules, a Phase 2a trial in compensated cirrhosis, and the Phase 2b biopsy trial, plus the earlier Janssen-era Phase 2 obesity trial under the JNJ-64565111 name. That is a normal development arc for a Phase 2b-stage MASH candidate.

2. Is efinopegdutide better than semaglutide at reducing liver fat?

In the one direct trial, yes, at the doses tested. The Phase 2a study, NCT04944992, randomised 145 adults with non-alcoholic fatty liver disease to efinopegdutide 10 mg (72) or semaglutide 1 mg (73) weekly for 24 weeks. Mean baseline BMI was 34.3 and mean liver fat content 20.3%; a third had type 2 diabetes.

Two caveats decide how much this means. Liver fat by imaging is a surrogate; the endpoints that earn approval are biopsy-based resolution of steatohepatitis and improvement in fibrosis, which is what the Phase 2b trial measures. And semaglutide has since won accelerated MASH approval as Wegovy on ESSENCE, with steatohepatitis resolution in 62.9% versus 34.3% on placebo at 72 weeks, at 2.4 mg. Efinopegdutide’s advantage on fat has not yet been shown to translate into an advantage on histology.

3. What are the side effects of efinopegdutide?

The Phase 2a trial’s posted results on ClinicalTrials.gov (NCT04944992) show any adverse event in 88.9% of the efinopegdutide group (64 of 72) versus 72.6% on semaglutide (53 of 73), and discontinuation for adverse events in 5.6% (4 of 72) on efinopegdutide versus none on semaglutide. The most common events, by incidence of 5% or higher in either arm, were nausea (27.8% efinopegdutide vs 31.5% semaglutide), diarrhea (16.7% vs 17.8%), constipation (16.7% vs 5.5%), vomiting (16.7% vs 15.1%), decreased appetite (16.7% vs 15.1%), abdominal pain (12.5% vs 2.7%), and upper abdominal pain (9.7% vs 1.4%). Glucagon agonism raises two class questions, heart rate and glucose, and the trial’s glycemic results in the diabetic subgroup are in the published paper. The Phase 2b trial, NCT05877547, prospectively records the percentage of participants with adverse events and the percentage discontinuing for them, and will be the first substantial safety dataset when it reports. The earlier Janssen-era Phase 2 obesity trial of the same molecule (as JNJ-64565111) showed the tolerability pattern common to this drug class: nausea and vomiting exceeded placebo and liraglutide at every efinopegdutide dose, and roughly 28% of participants did not complete the 26-week trial.

Merck disclosed in a June 2023 newsroom release, timed to that year’s EASL congress, that efinopegdutide had received FDA Fast Track designation for NASH; Fast Track allows more frequent FDA meetings and eligibility for accelerated approval or priority review, but is not itself an approval or a judgment on safety or efficacy.

4. What is the status of the Phase 2b trial?

The Phase 2b study, NCT05877547 (Merck’s internal number MK-6024-013), started June 23, 2023 and enrolled 381 adults with biopsy-confirmed precirrhotic MASH. Arms are efinopegdutide 4 mg, 7 mg, and 10 mg (each with a titration period, the 4 mg arm ramping from 2 mg for four weeks before the target dose), placebo, and semaglutide 2.4 mg (escalated from 0.25 mg), all weekly for 52 weeks. The primary endpoint is the percentage achieving MASH resolution without worsening of fibrosis at week 52; secondary endpoints include fibrosis-stage improvement without worsening of steatohepatitis and change in body weight, and the trial also tracks adverse-event and discontinuation rates as co-primary safety endpoints. ClinicalTrials.gov lists the trial as completed on December 29, 2025, with no results posted as of September 2026.

Merck has three smaller efinopegdutide trials in the registry. NCT06465186 (MK-6024-017) is a Phase 2a trial in 80 adults with compensated cirrhosis from MASH, randomised to efinopegdutide or placebo weekly for 28 weeks with monthly dose escalation over the first three months; it started July 12, 2024 and is active but no longer recruiting, with an estimated primary completion of August 2026. NCT06482112 (MK-6024-016) is a Phase 2a, open-label dosing-regimen study that compared weekly 10 mg, every-two-weeks 10 mg, and every-two-weeks 15 mg schedules in 124 adults with MASLD over 28 weeks of escalation, measuring liver fat reduction by MRI-PDFF at week 28; it completed enrollment June 27, 2025, with results posted June 1, 2026. NCT06701305 (MK-6024-015) is a Phase 1 single- and multiple-ascending-dose study in 48 healthy adults with obesity (BMI 29-38), run June 2024 to February 2025 to establish pharmacokinetics and an acetaminophen absorption marker; it also completed.

No Phase 3 trial has been registered. Merck’s public pipeline document for the first quarter of 2026 lists efinopegdutide (MK-6024) in Phase 2 for MASH, alongside the company’s other MASH and gastric programs.

5. Why does efinopegdutide have three names?

Janssen’s Phase 2 obesity trial (474 adults with BMI 35-50, no diabetes, 26 weeks) tested JNJ-64565111 at 5.0, 7.4, and 10.0 mg with no dose escalation against placebo and open-label liraglutide 3.0 mg. Placebo-adjusted weight loss was dose-dependent: 6.8% at 5.0 mg, 8.1% at 7.4 mg, and 10.0% at the 10.0 mg dose, versus 5.8% for liraglutide. Nausea and vomiting were more frequent in every JNJ-64565111 arm than on placebo or liraglutide, and only 343 of 474 participants (72.4%) completed the trial. Those tolerability numbers, not a lack of efficacy, are why Janssen returned the molecule to Hanmi in 2019.

Merck licensed the molecule in August 2020 in a deal worth $10 million upfront and up to $860 million in development, regulatory, and commercial milestones, plus double-digit royalties on any approved product; Merck took exclusive global rights while Hanmi kept an option to commercialize in Korea. Merck’s decision to relicense the molecule for MASH reflects the bet that glucagon agonism is worth more in the liver than on the scale. All three names refer to the same molecule, and ClinicalTrials.gov lists them together.

6. How does efinopegdutide compare with the other liver-focused agonists?

The pemvidutide and survodutide pages cover the other two. For a log, an investigational drug is entered like any other: product, date, milligrams, and site. How GLP-1 tracking works covers what to record.

7. Efinopegdutide FAQ

• What is efinopegdutide used for?

  Nothing yet; it is investigational. Merck is developing it for MASH, the liver disease formerly called NASH, where a 24-week trial cut liver fat 72.7% and body weight 8.5%. Earlier owners tested it for obesity and type 2 diabetes before Merck refocused it on the liver.

• Is efinopegdutide better than semaglutide?

  On liver fat at 24 weeks, yes, in one Phase 2a trial: a 72.7% relative reduction versus 42.3% on semaglutide 1 mg. On weight the two were similar, 8.5% versus 7.1%. That trial used a diabetes dose of semaglutide and measured liver fat by imaging, not the biopsy endpoints that decide approval. Semaglutide 2.4 mg has since won MASH approval as Wegovy; efinopegdutide's biopsy trial has not reported.

• What are the side effects of efinopegdutide?

  In the Phase 2a trial's posted results, any adverse event occurred in 88.9% on efinopegdutide versus 72.6% on semaglutide, and 5.6% discontinued for adverse events on efinopegdutide versus none on semaglutide. The most common events, at 5% or higher incidence in either arm, were nausea (27.8% vs 31.5%), diarrhea (16.7% vs 17.8%), constipation (16.7% vs 5.5%), vomiting (16.7% vs 15.1%), decreased appetite (16.7% vs 15.1%), abdominal pain (12.5% vs 2.7%), and upper abdominal pain (9.7% vs 1.4%). The Phase 2b trial records adverse-event and discontinuation rates as endpoints but has not posted results.

• Why does efinopegdutide have three names?

  Hanmi Pharmaceutical discovered it as HM12525A, licensed it to Janssen, which called it JNJ-64565111 and tested it for obesity and diabetes, then returned it. Merck licensed it in 2020 as MK-6024 and named it efinopegdutide. All three refer to the same molecule.

• Is efinopegdutide approved?

  No. Phase 2b is complete but unreported, and no Phase 3 has been registered. Merck's public pipeline document for the first quarter of 2026 lists efinopegdutide (MK-6024) in Phase 2 for MASH.

• What did Merck pay to license efinopegdutide?

  $10 million upfront plus up to $860 million in milestones and double-digit royalties, per the August 2020 deal with Hanmi Pharmaceutical (full terms above). Merck got exclusive global rights; Hanmi kept an option to commercialize in Korea.

• Does efinopegdutide have FDA Fast Track designation?

  Yes, for NASH, disclosed by Merck in June 2023. Fast Track speeds up FDA interactions and opens the door to accelerated approval or priority review; it is not an approval and does not mean the drug works or is safe.

8. Sources