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In the only head-to-head published, it cut liver fat by 72.7% at 24 weeks against 42.3% with semaglutide 1 mg.
Also known as: MK-6024 · GLP-1/glucagon receptor co-agonist
Part of the Metabolic & GLP-1 peptides cluster
Overview
Efinopegdutide (MK-6024) is an investigational once-weekly GLP-1/glucagon receptor co-agonist peptide being developed by Merck for metabolic dysfunction-associated steatohepatitis. In a phase 2a trial in fatty liver disease it reduced liver fat content by 72.7% at 24 weeks versus 42.3% with semaglutide 1 mg (Romero-Gómez et al., Journal of Hepatology 2023). Phase 2 trials in MASH and compensated cirrhosis are under way; it is not approved anywhere.
Source & context
Biological / chemical source: Synthetic engineered peptide co-agonist
Primary research or clinical context: Investigational (Merck) — phase 2 in metabolic dysfunction-associated steatohepatitis (MASH); not approved as of September 2026
What efinopegdutide is
Efinopegdutide, Merck's MK-6024, is a once-weekly injectable peptide that activates both the GLP-1 receptor and the glucagon receptor. It belongs to the same dual-agonist class as survodutide and mazdutide: the GLP-1 component supplies appetite suppression and glucose-dependent insulin release, while glucagon receptor activity adds hepatic fat oxidation and energy expenditure. Unlike those two, its development has been steered toward the liver — metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) — rather than obesity as the lead indication. Its full sequence and modifications have not been deposited in the public registries used by this site, so no residue-level structure is shown.
Mechanism: why a glucagon component for the liver
Glucagon receptor activation in the liver drives fatty-acid oxidation and lowers stored triglyceride, which is precisely the tissue and the process that MASLD involves. A selective GLP-1 agonist reduces liver fat mainly by reducing body weight; adding glucagon agonism targets the liver directly. The trade-off, shared across the class, is that glucagon raises glucose and heart rate, so the two activities must be balanced with the GLP-1 component dominant. The GLP-1 vs GIP vs glucagon guide on this site explains the receptor logic; the survodutide profile describes the same balance from the glucagon-scaffold side.
Clinical evidence: the phase 2a liver-fat trial
A phase 2a, randomised, active-comparator-controlled, open-label study enrolled 145 participants with MRI-estimated liver fat content of at least 10% (33.1% with type 2 diabetes; mean BMI 34.3 kg/m²; mean liver fat 20.3%) and randomised them 1:1 to efinopegdutide 10 mg or semaglutide 1 mg, both subcutaneous once weekly for 24 weeks after an 8-week titration (Romero-Gómez et al., Journal of Hepatology 2023). The least-squares mean relative reduction in liver fat at week 24 was 72.7% (90% CI 66.8–78.7) with efinopegdutide versus 42.3% (36.5–48.1) with semaglutide (p < 0.001). Body weight fell 8.5% versus 7.1% (p = 0.085). Slightly higher incidences of adverse events and drug-related adverse events were observed with efinopegdutide.
| Endpoint | Efinopegdutide 10 mg | Semaglutide 1 mg |
|---|---|---|
| Relative reduction in liver fat content | 72.7% | 42.3% |
| Body weight change | −8.5% | −7.1% |
| Participants | 72 | 73 |
How it ranks against other liver-fat therapies
A 2026 network meta-analysis of 39 randomised trials (3,311 participants) using MRI-PDFF ranked efinopegdutide among the most effective interventions for achieving a ≥30% decline in liver fat at 24 weeks, alongside semaglutide plus firsocostat and pegbelfermin (Koh et al., Hepatology 2026). A 2025 meta-analysis of 25 trials of GLP-1-based therapies found significant reductions in liver fat and histological improvements in steatosis, ballooning and inflammation across the class, with retatrutide showing the largest liver-fat effect and non-significant effects on fibrosis (Wang et al., Journal of Clinical Endocrinology & Metabolism 2025). Cross-trial rankings are indicative, not head-to-head evidence.
Development status as of September 2026
ClinicalTrials.gov lists seven studies: completed phase 2 trials in pre-cirrhotic MASH and an alternate-dosing study in MASLD, an active phase 2 trial in compensated cirrhosis due to MASH, and completed phase 1 studies in hepatic impairment and in healthy participants with obesity. No phase 3 trial had been registered and no regulator has approved efinopegdutide. Its evidence base is therefore one published comparative trial plus meta-analyses; histological MASH outcomes from the phase 2 programme had not been published in the sources reviewed here.
Efinopegdutide vs survodutide vs mazdutide
All three are GLP-1/glucagon dual agonists. Survodutide is glucagon-scaffold-based and has both obesity (phase 3) and MASH programmes; mazdutide is oxyntomodulin-based and is approved in China for weight management. Efinopegdutide is the one being developed primarily as a liver drug, and it is the only one with a published direct comparison against semaglutide on liver fat. Weight loss in its trial (8.5% at 24 weeks) sits in the range reported for the class at similar durations, but it has not been tested for obesity as a primary indication.
Structure & chemistry
Molecular identity & reference confidence
Reference mass unavailable
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Efinopegdutide (source record; form not independently established)
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- Receptors
- GLP-1 receptor and glucagon receptor (dual agonist)
- Status
- Investigational — phase 2 (MASH, compensated MASH cirrhosis); not approved as of September 2026
Chemistry values: curated profile.
Clinical development snapshot
ClinicalTrials.gov lists 7 registered studies with “Efinopegdutide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT06465186 | A Clinical Study of Efinopegdutide in People With Compensated Cirrhosis Due to Steatohepatitis (MK-6024-017) | Phase 2 | completed | 2026-09-21 |
| NCT06482112 | Alternate Dosing Study of MK-6024 in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MAS | Phase 2 | completed | 2026-06-01 |
| NCT05877547 | A Clinical Study of Efinopegdutide in Participants With Precirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-6 | Phase 2 | completed | 2026-01-12 |
| NCT06052566 | A Study of Efinopegdutide in Participants With Hepatic Impairment (MK-6024-014) | Phase 1 | completed | 2025-10-22 |
| NCT06701305 | A Study of Efinopegdutide in Healthy Obese Participants (MK-6024-015) | Phase 1 | completed | 2025-02-26 |
| NCT06836037 | A Clinical Study of Efinopegdutide (MK-6024) in Healthy Chinese Volunteers (MK-6024-011) | Phase 1 | completed | 2025-02-21 |
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Efinopegdutide
What is Efinopegdutide?+
Efinopegdutide (MK-6024) is an investigational once-weekly GLP-1/glucagon receptor co-agonist peptide being developed by Merck for metabolic dysfunction-associated steatohepatitis. In a phase 2a trial in fatty liver disease it reduced liver fat content by 72.7% at 24 weeks versus 42.3% with semaglutide 1 mg (Romero-Gómez et al., Journal of Hepatology 2023). Phase 2 trials in MASH and compensated cirrhosis are under way; it is not approved anywhere.
What Canadian product status is recorded for Efinopegdutide?+
Canadian product status for Efinopegdutide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Efinopegdutide?+
Efinopegdutide is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.
What is efinopegdutide?+
An investigational once-weekly GLP-1/glucagon receptor co-agonist peptide (MK-6024) from Merck, in phase 2 development for MASH.
How much did efinopegdutide reduce liver fat?+
By 72.7% at 24 weeks in a phase 2a trial, versus 42.3% with semaglutide 1 mg in the same study.
Is efinopegdutide approved?+
No. As of September 2026 it is in phase 2 trials and not approved in any country.
How does efinopegdutide differ from semaglutide?+
Semaglutide activates only the GLP-1 receptor; efinopegdutide also activates the glucagon receptor, which drives fat oxidation in the liver. In the direct comparison it reduced liver fat more, with similar weight loss.
Is efinopegdutide for weight loss?+
Its development targets fatty liver disease. Weight loss of 8.5% at 24 weeks was a secondary observation in the phase 2a trial.
Related peptides
References & further reading
- 1.Wen et al. (2024). Comparative Efficacy of Semaglutide Versus Liraglutide or Efinopegdutide on Weight Loss in Obese Patients: A Systematic Review and Meta-Analysis. Cureus
- 2.Romero-Gómez et al. (2023). 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
- 3.Di Prospero et al. (2021). 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
- 4.Alba et al. (2021). 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
- 5.Koh B et al. (2026). Comparative efficacy of pharmacologic therapies for MASH in reducing liver fat content: Systematic review and network meta-analysis. Hepatology
- 6.Wang Y et al. (2025). Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab
- 7.Polyzos SA et al. (2023). Peptide Polyagonists for the Treatment of Nonalcoholic Fatty Liver Disease. Curr Pharm Des