Efinopegdutide
A GLP-1/glucagon dual agonist repurposed for fatty liver disease
Efinopegdutide is an investigational once-weekly drug that activates both GLP-1 and glucagon receptors. Tested first for obesity, where it was not clearly better than existing drugs, it is now being developed by MSD for fatty liver disease, after cutting liver fat by 72.7% against 42.3% for semaglutide in a phase 2a trial.
What is it?
Combining GLP-1 with glucagon activity is a way of adding energy burning and liver fat breakdown to GLP-1's appetite effects. Efinopegdutide, under the code JNJ-64565111, was tested by Janssen for obesity: in 474 people without diabetes it lowered weight by 6.8% to 10.0% more than placebo at 26 weeks, against 5.8% for liraglutide, but with more nausea and vomiting. In people with type 2 diabetes it did not lower HbA1c and nudged fasting glucose up.
The liver was where it stood out. In a phase 2a trial of 145 people with fatty liver disease, efinopegdutide cut liver fat by 72.7% at 24 weeks against 42.3% with semaglutide, while weight loss was similar (8.5% against 7.1%). MSD has since run a 381-participant phase 2b trial in precirrhotic MASH and a trial in compensated cirrhosis, both listed as completed.
It is not approved anywhere. Gastrointestinal side effects are the main tolerability issue, as with other drugs in this class, and its glucagon activity can raise blood glucose, which matters for people with diabetes.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Published Research
Trials of efinopegdutide, from their PubMed abstracts.
Phase 2a: fatty liver vs semaglutide
In 145 people with NAFLD, liver fat fell by 72.7% at 24 weeks with efinopegdutide against 42.3% with semaglutide (p < 0.001); body weight fell 8.5% against 7.1% (p = 0.085).
Obesity without diabetes
In 474 participants, placebo-subtracted weight loss at 26 weeks was 6.8%, 8.1% and 10.0% across three doses against 5.8% for open-label liraglutide, with more nausea and vomiting than placebo or liraglutide.
Obesity with type 2 diabetes
In 195 participants, placebo-subtracted weight loss at 12 weeks was 4.6% to 7.2%, but HbA1c did not change and fasting glucose and insulin rose slightly, with more gastrointestinal adverse events.
Against semaglutide for weight
A meta-analysis of direct comparisons found semaglutide produced more weight loss than liraglutide but no significant difference from efinopegdutide; all were mostly well tolerated, with gastrointestinal side effects.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
No label; it is investigational.
Legal Status
Efinopegdutide is investigational.
Frequently Asked Questions
?What is efinopegdutide?
An investigational once-weekly drug that activates GLP-1 and glucagon receptors, now in development for fatty liver disease (MASH).
?How does it compare with semaglutide?
In a 145-person phase 2a trial, it cut liver fat by 72.7% against 42.3% for semaglutide, with similar weight loss.
?Is efinopegdutide approved?
No. Phase 2b trials in MASH and cirrhosis are listed as completed, but it is not approved anywhere, and products sold online under its name are unverified.
?Why did its obesity programme not continue?
In Janssen's trials it lowered weight more than placebo but caused more nausea and vomiting, and in type 2 diabetes it did not improve HbA1c and raised fasting glucose slightly.
?Is it being tested in liver cirrhosis?
Yes. An 85-participant trial in compensated cirrhosis due to steatohepatitis is registered on ClinicalTrials.gov as completed, alongside a 381-participant phase 2b trial in precirrhotic MASH; results had not been published in a paper we could find.
References
- [registry] ClinicalTrials.gov API v2, read October 3, 2026: NCT04944992 (phase 2a NAFLD vs semaglutide, 145 participants, completed), NCT05877547 (phase 2b precirrhotic MASH, 381, completed), NCT06465186 (compensated cirrhosis, 85, completed), NCT06482112 (alternate dosing, 124, completed), NCT06052566 (hepatic impairment, phase 1).
- [clinical-trial] Romero-Gómez M, et al. "A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease." J Hepatol, 2023;79(4):888-897. PMID: 37355043.
- [clinical-trial] Alba M, et al. "Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with obesity without type 2 diabetes mellitus: A randomized dose-ranging study." Clin Obes, 2021;11(2):e12432. PMID: 33475255.
- [clinical-trial] Di Prospero NA, et al. "Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with type 2 diabetes mellitus and obesity: A randomized dose-ranging study." Clin Obes, 2021;11(2):e12433. PMID: 33475251.
- [pubmed] Wen J, et al. "Comparative Efficacy of Semaglutide Versus Liraglutide or Efinopegdutide on Weight Loss in Obese Patients: A Systematic Review and Meta-Analysis." Cureus, 2024;16(12):e75304. PMID: 39776746.
Sources & Citations
Studies were read from their PubMed records; trial registrations from ClinicalTrials.gov, read October 3, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.