Evidence Grade E — Very limited evidence. 7 published studies. 7 registered clinical trials.
Medically reviewed by a licensed medical professional
Efinopegdutide is a dual GLP-1/glucagon agonist in Phase II development, jointly developed by Hanmi Pharmaceutical and MSD (Merck). Its standout result is a head-to-head trial against semaglutide showing dramatically greater liver fat reduction — making it a candidate for fatty liver disease (MASH) treatment.
Efinopegdutide is also known by these brand and alternate names:
7 published studies: 6 human, 0 animal, 0 in-vitro, 5 reviews
Efinopegdutide is in Phase II development (not yet approved). A Phase IIa head-to-head trial against semaglutide (145 patients) showed significantly greater liver fat reduction (72.7% versus 42.3%, P<0.001) despite similar overall weight loss. A Phase IIb MASH trial is ongoing.
The head-to-head superiority over semaglutide on liver fat — the key pathological feature of MASH — positions efinopegdutide for the liver disease indication. Whether the liver fat advantage translates to superior histological outcomes will be determined by the Phase IIb trial.
Efinopegdutide combines GLP-1 receptor activation (appetite suppression, glucose control) with glucagon receptor activation (hepatic fat oxidation, energy expenditure). The PEGylated Fc-fusion design extends the half-life for less frequent dosing. The glucagon component's direct liver fat-burning effect may explain the superior liver fat reduction compared to GLP-1-only approaches.
A Phase IIa head-to-head trial (145 patients) showed significantly greater liver fat reduction with efinopegdutide compared to semaglutide (72.7% versus 42.3%) despite similar overall weight loss. This suggests the glucagon component provides liver-specific fat burning above and beyond what weight loss alone achieves. The development focus has pivoted away from obesity (likely due to the increasingly competitive landscape) toward MASH, where the liver-specific advantage positions it more distinctly. A Phase IIb MASH trial with liver biopsy endpoints is ongoing. Key limitations include the small Phase IIa sample size and the absence of biopsy-confirmed MASH outcomes in completed trials.
PeptideTrace tracks 7 registered clinical trials for Efinopegdutide sourced from ClinicalTrials.gov.
Alternate Dosing Study of MK-6024 in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (MK-6024-016)
A Clinical Study of Efinopegdutide in People With Compensated Cirrhosis Due to Steatohepatitis (MK-6024-017)
A Study of Efinopegdutide in Healthy Obese Participants (MK-6024-015)
A Study of Efinopegdutide in Participants With Hepatic Impairment (MK-6024-014)
A Clinical Study of Efinopegdutide in Participants With Precirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-6024-013)
Efinopegdutide (MK-6024/HM12525A) is a PEGylated oxyntomodulin analog conjugated to an IgG4 Fc domain for extended half-life, developed using Hanmi Pharmaceutical's LAPS technology platform. CAS number: 2055640-93-0. The compound was originally licensed through Johnson and Johnson and subsequently sublicensed to Merck for development in MASH. Once-weekly subcutaneous injection. Merck has strategically pivoted development away from obesity and T2D toward a MASH-focused strategy, and the compound holds FDA Fast Track designation for MASH.
Efinopegdutide provides dual agonism at GLP-1R and GCGR through its oxyntomodulin-based peptide backbone. The GLP-1 component delivers appetite suppression and glycemic control, while the glucagon component directly promotes hepatic fat oxidation, reduces de novo lipogenesis, and increases energy expenditure. The IgG4 Fc conjugation via LAPS technology provides the extended half-life necessary for weekly dosing.
Phase 2a NAFLD (NCT04944992; N=145; Journal of Hepatology 2023): liver fat content reduction of 72.7% with efinopegdutide 10 mg versus 42.3% with semaglutide 1 mg (P<0.001 for difference). Weight loss: -8.5% versus -7.1% with semaglutide (P=0.085, not significant). Phase 2b MASH trial (NCT05877547; N approximately 300; 52 weeks) is currently active with enrollment completed. The obesity and T2D indications have been discontinued as part of the strategic pivot to focus exclusively on MASH.
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Semaglutide is one of the most extensively studied peptide medications available today, with clinical trial data spanning over 50,000 patients. It is sold as Ozempic for type 2 diabetes (approved 2017), Rybelsus as an oral tablet for diabetes (approved 2019), and Wegovy for weight management (approved 2021). Wegovy has since received additional approvals for reducing heart attack and stroke risk, for use in adolescents aged 12 and older, and for liver disease related to obesity. In clinical trials, patients taking Wegovy lost an average of 14.9% of their body weight over 68 weeks, and the SELECT trial demonstrated a 20% reduction in major cardiovascular events such as heart attack and stroke. Research is now exploring its potential in early Alzheimer's disease. The main side effects are gastrointestinal, particularly nausea, and a key limitation is that most weight tends to return after stopping treatment.
Bimagrumab is in Phase II/III development (not yet approved). A Phase II trial (75 patients with type 2 diabetes and obesity) showed 20.5% fat mass reduction with 3.6% lean mass increase — essentially reshaping body composition without net appetite suppression. The BELIEVE Phase IIb trial (507 patients) showed that bimagrumab plus semaglutide achieved 22% weight loss with the weight lost being 88% fat — significantly better body composition than semaglutide alone. Bimagrumab is not a peptide. Its strategic significance is as a combination partner to address the muscle loss problem inherent in weight loss with current obesity drugs. Eli Lilly's acquisition positions it alongside tirzepatide.
Pemvidutide is in Phase II/III development (not yet approved). In the MOMENTUM Phase II trial (391 patients, 48 weeks), the 2.4 mg dose achieved 15.6% weight loss. Body composition analysis showed 78% of weight lost was fat mass, with only 22% lean mass — a favourable ratio. A Phase IIb MASH trial (212 patients) showed MASH resolution in up to 75% of patients at the highest dose. Pemvidutide's balanced receptor profile and no-titration dosing regimen represent potential practical advantages. The high rate of MASH resolution in Phase II positions it as a candidate for liver disease indications alongside obesity.
Evidence Reviews
Timelines
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
