Efinopegdutide: the molecule Merck is studying for fatty liver disease

It is not a short peptide. According to the US FDA's substance registry (GSRS), it is:

• a 30-amino-acid peptide, an analogue of oxyntomodulin (a natural gut hormone),
• joined through a 10 kDa PEG linker to
• a piece (Fc) of human IgG4 antibody, as a dimer.

It is made in bacteria (E. coli). The estimated molecular weight is about 53,400 Da, but the FDA record notes that the PEG portion may not be included in the calculation, so the figure is uncertain. Hanmi, which designed it, licensed it first to Janssen and then to Merck (4 August 2020).

Administration in the studies was subcutaneous, mostly once weekly, and in one study every other week.

Seven trials are registered on ClinicalTrials.gov and none in Phase 3. In Merck's 5 August 2026 pipeline it appears in Phase 2 for MASH. Merck received Fast Track designation from the FDA for NASH (announcement 2023).

• NCT05877547: Focus: MASH with F2–F3 fibrosis, 52 weeks · Phase: 2b · Participants: 381 · Status: Completed 29 Dec 2025, no results posted
• NCT06465186: Focus: MASH with cirrhosis, 28 weeks · Phase: 2a · Participants: 85 · Status: Completed 3 Aug 2026, no results
• NCT06482112: Focus: Fatty liver, regimen comparison · Phase: 2a · Participants: 124 · Status: Completed, results in the registry
• NCT04944992: Focus: Fatty liver · Phase: 2a · Participants: 145 · Status: Completed, published
• NCT03486392: Focus: Obesity (Janssen) · Phase: 2 · Participants: 474 · Status: Completed, published
• NCT03586830: Focus: Obesity and diabetes (Janssen) · Phase: 2 · Participants: 195 · Status: Completed, published

The Phase 2b MASH trial (NCT05877547) has as its primary question "MASH resolution without worsening of fibrosis at week 52". It has finished, but we found neither posted nor published results.

Fatty liver, 24 weeks — peer-reviewed (Journal of Hepatology 2023, PMID 37355043). Among 145 participants, at the 10 mg dose, liver fat fell by 72.7% (90% confidence interval 66.8 to 78.7) and body weight by 8.5%. The study was open-label and had a second arm with another compound; that arm's data are not presented here and no comparison is made. At baseline, mean BMI was 34.3 and liver fat 20.3%.

Regimen comparison, 28 weeks — results in the registry, not peer-reviewed. Liver-fat reduction was 67.8% with 10 mg weekly, 54.4% with 10 mg every two weeks, and 42.1% with 15 mg every two weeks. Weight change was −7.5%, −3.9% and −4.1% respectively.

Obesity, 26 weeks (Janssen) — peer-reviewed (Clinical Obesity 2021, PMID 33475255). Among 474 participants with a BMI of 35 to 50, without step-up dosing, weight change beyond placebo was −6.8% (5.0 mg), −8.1% (7.4 mg) and −10.0% (10.0 mg).

Obesity and type 2 diabetes, 12 weeks (Janssen) — peer-reviewed (Clinical Obesity 2021, PMID 33475251). Weight change beyond placebo was −4.6%, −5.9% and −7.2%. Glycated haemoglobin did not change, while fasting glucose and insulin rose slightly.

Clinical-trial facts, not usage instructions. Efinopegdutide is an investigational compound without approval. All doses are subcutaneous.

• Phase 2a (fatty liver): 2.4 mg from week 1 to 3, 5.0 mg from week 4 to 7, and 10.0 mg from week 8 to 24, once weekly (registry NCT04944992 and J Hepatol 2023).
• Phase 2b (MASH): three target doses, 4, 7 and 10 mg. The dose rose every 4 weeks, from 2 mg toward 4, 7 and 10 mg. The 10 mg group stayed at 10 mg for 40 weeks.
• Regimen comparison: 10 mg weekly, 10 mg every two weeks, and 15 mg every two weeks. 15 mg is the highest dose we found in a registry record.
• Janssen studies: fixed doses of 5.0, 7.4 and 10.0 mg weekly, without step-up.
• Pharmacokinetic study: a single 7 mg dose.

In the pharmacokinetic study (NCT06052566, results in the registry, 22 participants), half-life after a single 7 mg dose was 115 hours (about 4.8 days) in healthy participants, and 146 to 149 hours in people with liver impairment. There is no peer-reviewed publication.

In the published Phase 2a study, gastrointestinal events were more frequent in the efinopegdutide group. Nausea 20 of 72, vomiting 12 of 72, diarrhoea 12 of 72, constipation 12 of 72. The paper states the difference was mainly due to gastrointestinal events.

In the regimen-comparison study, nausea was reported by 33.3% to 47.6% and 5.1% to 9.5% stopped because of an adverse event.

In the Janssen studies, where the dose was not stepped up, nausea reached 50.8% to 67.8% and vomiting 20.3% to 54.2%, versus 6.7% and 0% on placebo. These are different studies and are not directly comparable with the others.

Trials excluded people with a history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, pancreatitis, type 1 diabetes, and a recent heart attack or stroke. There is no official contraindication list, because there is no approved medicine.

• The results of the large MASH trial. It finished in December 2025 and we found no published data on MASH or fibrosis resolution. There are no data on which to claim anything.
• The results in MASH with cirrhosis.
• The exact molecular weight, because the PEG portion may not be counted.
• Whether a Phase 3 will happen. None is registered.

This content is educational and research-oriented. Efinopegdutide is an investigational compound, is not approved as a medicine, and is not intended for human use. This is not medical advice.