Efinopegdutide
Efinopegdutide (MK-6024), GLP-1 and glucagon receptor dual agonist
Written by Aaron CuhaReviewed Sep 2026
Also known as: MK-6024, HM12525A, JNJ-64565111
Beat semaglutide on liver fat in a randomised head to head, cutting it 72.7 percent against 42.3 percent, while the weight difference was not significant. Adding glucagon does something to the liver that GLP-1 alone does not.
Overview
Most dual agonists on this site pair GLP-1 with GIP. This one pairs it with glucagon, which sounds wrong to anyone who knows glucagon raises blood sugar, and the logic is worth following. Glucagon receptor agonism acts directly on the liver to stimulate fatty acid oxidation and suppress lipogenesis. Pair it with enough GLP-1 to control the glycaemic downside and you get a drug aimed at the liver rather than at the scale.
The head to head result supports exactly that reading. Against semaglutide 1 mg over 24 weeks in 145 people with fatty liver disease, efinopegdutide reduced liver fat content by 72.7 percent against 42.3 percent, p below 0.001. Weight loss was 8.5 percent against 7.1 percent, p equals 0.085, not significant. So the liver effect was much larger while the weight effect was not, which is the signal that something other than weight loss is happening.
Mechanism of action
A co-agonist at the GLP-1 and glucagon receptors, built on a long-acting Fc-based scaffold. GLP-1 receptor agonism reduces food intake and improves glycaemic control in the usual way. Glucagon receptor agonism raises hepatic fatty acid oxidation and reduces de novo lipogenesis, and also increases energy expenditure, which is the intended mechanism for the liver fat effect. The glycaemic risk of glucagon agonism is the reason these drugs are balanced rather than glucagon-dominant.
Human evidence
One randomised active-comparator trial, which is a stronger design than most drugs at this stage carry, plus an ongoing programme in steatohepatitis. No outcome data.
- 145 participants, 24 weeks, head to head against semaglutide 1 mg rather than against placebo.
- Liver fat content fell 72.7 percent against 42.3 percent on semaglutide, p < 0.001.
- Weight fell 8.5 percent against 7.1 percent, p = 0.085, not significant. The liver effect is therefore not explained by a weight difference, which is the trial's most useful feature.
- Adverse events were slightly higher on efinopegdutide, primarily gastrointestinal, the usual pattern for this class.
- One-third of participants had type 2 diabetes, and randomisation was stratified on that.
What this does not tell you: The comparator dose deserves the same scrutiny this site applies elsewhere: semaglutide 1 mg is a diabetes dose, well below the 2.4 mg used for obesity, so the comparison is not against semaglutide at its best. The trial was open-label, which matters less for an MRI-measured endpoint than for a reported one. And liver fat content is a biomarker. It predicts risk and it is not the same as fibrosis, cirrhosis or death, none of which this trial measured. 145 people over 24 weeks cannot speak to any of those.
Reading the research record
This trial is a good example of why this site reports head to head results rather than refusing to compare. A placebo-controlled trial showing a 72.7 percent reduction in liver fat would be interesting and nearly uninterpretable, because GLP-1 drugs already reduce liver fat through weight loss. Running it against semaglutide, and finding the liver effect much larger while the weight effect was not significant, is what isolates the glucagon contribution. That is a trial result, not an opinion, and it gets reported as one.
What it does not license is a ranking. Semaglutide at 1 mg is not semaglutide at its approved obesity dose, and a biomarker win over 24 weeks in 145 people is not evidence that anyone's liver disease progressed more slowly.
The evidence, charted
Fig. 1 · evidence composition
3of 3 citations (100%) are in people
Every citation cited here is Human work; no other study type is cited on this page. This count is of our own citation list and understates any literature larger than the sources we cite.
Fig. 2 · evidence over time
Citations here span just two years, 2023 and 2026.
Too few distinct publication years on this page to plot as a timeline.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2023
A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease
145 participants with liver fat content of 10 percent or more, randomised 1:1 to efinopegdutide 10 mg or semaglutide 1 mg weekly for 24 weeks, open-label. Mean baseline BMI 34.3 and liver fat 20.3 percent; 33.1 percent had type 2 diabetes. Relative reduction in liver fat 72.7 percent (90% CI 66.8 to 78.7) against 42.3 percent (90% CI 36.5 to 48.1), p < 0.001. Body weight reduction 8.5 percent against 7.1 percent, p = 0.085, not significant. Slightly higher adverse events on efinopegdutide, mainly gastrointestinal.
Journal of Hepatology - Human2023
A study of efinopegdutide in participants with non-alcoholic fatty liver disease
The registry record for the head to head trial above.
ClinicalTrials.gov - Human2026
A study of efinopegdutide in participants with metabolic dysfunction-associated steatohepatitis
The follow-on programme in steatohepatitis, which is the disease stage where liver fat matters clinically. Liver fat is a biomarker; fibrosis progression and liver outcomes are not.
ClinicalTrials.gov
Frequently asked questions
Is it better than semaglutide?
On liver fat over 24 weeks, in 145 people, against semaglutide at 1 mg, yes and by a wide margin: 72.7 percent against 42.3 percent. On weight the difference was not significant. And 1 mg is a diabetes dose rather than the 2.4 mg used for obesity, so this is not a comparison against semaglutide at its strongest.
Why add glucagon, which raises blood sugar?
Because glucagon receptor agonism acts on the liver directly, increasing fatty acid oxidation and reducing fat synthesis, and it raises energy expenditure. The GLP-1 half is what keeps blood glucose controlled. The trial suggests the combination does something to the liver that GLP-1 alone does not.
Does it treat liver disease?
Unknown. It reduces liver fat, which is a biomarker. Whether that changes fibrosis progression, cirrhosis or death has not been tested, and that is the programme now running in steatohepatitis.
Can I get it?
No. It is investigational and not approved anywhere.