Merck’s efinopegdutide achieved 63% MASH resolution in its Phase 2b trial, with fibrosis improvement and results across three doses at Week 52.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Merck reported positive Phase 2b results for efinopegdutide (MK-6024), an investigational dual glucagon-like peptide-1 (GLP-1) and glucagon receptor co-agonist, in adults with metabolic dysfunction-associated steatohepatitis (MASH) and stage F2–F3 liver fibrosis. The study met its primary endpoint, with MASH resolution rates reaching 63% at the 7 mg dose compared with 13% with placebo.
The findings from the MK-6024-013 trial (NCT05877547) were presented during a late-breaking abstract session at The Liver Meeting and published in The Lancet on November 9, 2026.
Primary Histological Efficacy and MASH Resolution
The 52-week Phase 2b trial evaluated once-weekly subcutaneous efinopegdutide across three target doses (4 mg, 7 mg and 10 mg) against placebo, alongside an open-label semaglutide 2.4 mg active reference arm. The primary endpoint assessed the proportion of participants achieving MASH resolution without worsening of liver fibrosis at Week 52. Histological outcomes were evaluated using the Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN) scoring system through blinded independent central review (BICR).
At Week 52, efinopegdutide demonstrated statistically significant improvements in MASH resolution across all three evaluated doses compared with placebo (p<0.0001 for all doses):
- Efinopegdutide 7 mg: 63%
- Efinopegdutide 10 mg: 61%
- Efinopegdutide 4 mg: 56%
- Placebo: 13%
Non-Linear Dose Response and Efficacy Plateau
The 7 mg group recorded the highest numerical MASH resolution rate. However, increasing the dose to 10 mg did not produce an additional improvement in histological resolution. This non-linear response suggests that higher doses did not necessarily translate into greater efficacy within the evaluated dose range. The findings make the 7 mg dose particularly relevant for further clinical evaluation, although additional studies will be needed to establish the most appropriate dose.
Fibrosis Improvement and Active Reference Results
The key secondary histological endpoint assessed improvement in liver fibrosis by at least one stage without worsening of steatohepatitis.
At Week 52, fibrosis improvement was reported in 43% of participants receiving 4 mg, 52% receiving 7 mg and 34% receiving 10 mg, compared with 21% receiving placebo.
Meeting results also reported fibrosis endpoint differences versus placebo that were statistically significant for the 4 mg (p=0.004) and 7 mg (p<0.001) groups, but not for the 10 mg group (p=0.072).
The open-label semaglutide 2.4 mg reference arm recorded MASH resolution in 53% of participants and fibrosis improvement in 25%. These results provide additional context for the trial findings but do not establish comparative superiority because the study was not designed as a formal head-to-head efficacy comparison.
Dual-Receptor Mechanism and Development Status
Efinopegdutide combines GLP-1 receptor agonism with glucagon receptor activation. While GLP-1 activity contributes to appetite regulation and metabolic control, glucagon receptor activation is intended to enhance energy expenditure, influence lipid metabolism and produce direct anti-steatotic effects in the liver.
The dual-receptor approach is being investigated as a potential strategy to address metabolic dysfunction and hepatic fat accumulation in MASH.
Efinopegdutide has received Fast Track designation from the U.S. Food and Drug Administration (FDA). The investigational therapy is being developed under an exclusive licensing agreement between Merck and Hanmi Pharmaceutical. The designation does not constitute marketing approval.
Safety, Tolerability and Dose Escalation
Efinopegdutide was administered using a dose-escalation regimen, with doses increased every four weeks until participants reached their assigned target dose.
Gastrointestinal adverse events included nausea, diarrhea and vomiting. Nausea occurred in 29%, 39% and 44% of participants receiving efinopegdutide 4 mg, 7 mg and 10 mg, respectively, compared with 39% with semaglutide and 11% with placebo.
Adverse-event-related treatment discontinuations occurred in 3% of the 4 mg group, 4% of the 7 mg group and 11% of the 10 mg group, compared with 1% in both reference groups.
The higher nausea and discontinuation rates at 10 mg are relevant to dose selection. Together with the efficacy findings, the 7 mg group demonstrated the most favorable observed benefit-risk profile among the evaluated doses.
Trial Design and Clinical Implications
The study enrolled 386 adults with biopsy-confirmed MASH and F2 or F3 fibrosis. Of these, 381 participants were randomized and treated: 77 received 4 mg, 77 received 7 mg, 79 received 10 mg, 79 received placebo and 69 received open-label semaglutide 2.4 mg. Overall, 349 participants (92%) completed the study.
Clinical interpretation
Efinopegdutide achieved its primary histological endpoint across all three evaluated doses, while the 7 mg group recorded the highest MASH resolution and fibrosis improvement rates. The absence of a statistically significant fibrosis response at 10 mg, alongside higher gastrointestinal adverse events and treatment discontinuations, highlights the importance of balancing efficacy and tolerability.
Further clinical evaluation will be necessary to establish the durability of these histological responses, long-term safety and whether the observed improvements translate into reductions in cirrhosis, liver failure and other liver-related clinical complications.
References
Merck Announces Positive Results from Phase 2b Trial of Efinopegdutide in Adults with Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Stage 2–3 Fibrosis, Merck, 09 November 2026
A Clinical Study of Efinopegdutide in Participants With Precirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-6024-013), ClinicalTrials.gov ID NCT05877547
Lawitz E, Wong V, Shankar R et al., Efficacy and safety of efinopegdutide in adults with metabolic dysfunction-associated steatohepatitis and stage 2–3 fibrosis: a phase 2b, randomised, placebo-controlled study, The Lancet, Published November 9, 2026, https://doi.org/10.1016/S0140-6736(26)02043-X
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.