Efinopegdutide

An investigational once-weekly GLP-1/glucagon receptor dual agonist, an oxyntomodulin-derived peptide conjugated to an immunoglobulin Fc fragment, originated by Hanmi, trialed in obesity by Janssen, and developed since 2020 by Merck for metabolic dysfunction-associated steatohepatitis.

Also referenced as: MK-6024, HM12525A, JNJ-64565111, LAPS-GLP/GCG

Also appears in: Weight loss

COA Public product evidence No certificate records are bound to a tracked Efinopegdutide product page A record counts here only when a vendor publishes a certificate against one of its own tracked Efinopegdutide product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

---

What is Efinopegdutide?

Efinopegdutide is an Fc-conjugated dual agonist peptide: a synthetic, modified oxyntomodulin analog with agonist activity at both the GLP-1 receptor and the glucagon receptor, attached through a polyethylene glycol linker to a human immunoglobulin Fc fragment. The carrier comes from Hanmi Pharmaceutical’s LAPSCOVERY long-acting platform, which is why the molecule has been dosed once weekly from its first clinical studies onward. It began life as HM12525A (LAPS-GLP/GCG) at Hanmi, was licensed to Janssen in November 2015 and ran through phase 2 obesity trials as JNJ-64565111, and since August 2020 has been developed by Merck (MSD outside North America) as MK-6024 for metabolic dysfunction-associated steatohepatitis (MASH), the condition formerly called NASH. It is a large biologic conjugate rather than a short synthetic peptide, and it is not a research-market product.

How it works

• Balanced incretin and glucagon signaling from one oxyntomodulin scaffold. Oxyntomodulin is a native proglucagon-derived gut peptide that activates both GLP-1 and glucagon receptors; engineered analogs like efinopegdutide keep that dual activity while adding stability and half-life (Zhihong et al., Peptides, 2023;162:170955; Novikoff and Müller, Peptides, 2023;165:171003).
• GLP-1 receptor agonism. In the Janssen phase 2 program, weekly dosing produced dose-dependent placebo-subtracted weight loss of up to 10.0% at 26 weeks, exceeding the 5.8% seen with daily liraglutide 3 mg in the same trial (Alba et al., Clinical Obesity, 2021).
• Glucagon receptor agonism in the liver. Hepatocyte glucagon signaling stimulates fatty acid oxidation and suppresses lipogenesis, which is the rationale for a liver-fat benefit beyond what weight loss alone delivers; in the phase 2a head-to-head, efinopegdutide reduced liver fat by 72.7% versus 42.3% with semaglutide 1 mg despite similar weight change (Romero-Gómez et al., Journal of Hepatology, 2023).
• Blunted glucose lowering. In people with type 2 diabetes, 12 weeks of treatment reduced weight with no change in HbA1c, a slight numerical rise in fasting insulin, and numerical increases in fasting plasma glucose at the 5.0 and 7.4 mg doses, consistent with glucagon-receptor engagement offsetting the incretin effect (Di Prospero et al., Clinical Obesity, 2021).

Research status

Obesity and diabetes (Janssen era, discontinued). Two phase 2 dose-ranging trials were published together in Clinical Obesity 11(2), 2021. In 474 adults with class II/III obesity and no diabetes (NCT03486392), placebo-subtracted weight change at week 26 was -6.8%, -8.1% and -10.0% for the 5.0, 7.4 and 10.0 mg weekly arms versus -5.8% for open-label liraglutide 3 mg, but only 343 participants (72.4%) completed treatment, and nausea and vomiting were markedly more frequent than with placebo or liraglutide (Alba et al., Clinical Obesity, 2021;11(2):e12432). In 195 dosed adults with type 2 diabetes and obesity (NCT03586830), weight fell by -4.6%, -5.9% and -7.2% placebo-subtracted at week 12 with no HbA1c reduction (Di Prospero et al., Clinical Obesity, 2021;11(2):e12433). Janssen wound the program down in mid-2019: its Japanese phase 1 study (NCT03618160) was terminated on June 21, 2019 because, in the registry’s words, the results of the leading phase 2 trials did not meet all desired endpoints, and the rights reverted to Hanmi. The type 2 diabetes and obesity indications were not pursued further.

MASLD/MASH (Merck era, active). Merck licensed the compound from Hanmi on August 4, 2020 and refocused it on fatty liver disease. The phase 2a MK-6024-001 study (NCT04944992) randomized 145 adults with NAFLD and at least 10% liver fat to efinopegdutide 10 mg or semaglutide 1 mg weekly for 24 weeks; relative liver-fat reduction by MRI-PDFF was 72.7% versus 42.3% (p < 0.001) and weight loss was 8.5% versus 7.1% (p = 0.085). The posted ClinicalTrials.gov results show adverse events in 88.9% versus 72.6% of participants and discontinuation for an adverse event in 5.6% versus 0%, an imbalance the authors attribute mainly to gastrointestinal events (Romero-Gómez et al., Journal of Hepatology, 2023;79(4):888-897). On June 12, 2023, Merck announced that the FDA had granted Fast Track designation for MK-6024 in NASH and that the phase 2a data had informed the design of a phase 2b study it planned to start that month.

The phase 2b MK-6024-013 study (NCT05877547) enrolled 381 adults with precirrhotic MASH in a triple-blind, placebo-controlled design comparing efinopegdutide 4, 7 and 10 mg weekly against placebo for 52 weeks, with a semaglutide 2.4 mg active-comparator arm; the primary efficacy endpoint is MASH resolution without worsening of fibrosis at week 52. The trial started June 23, 2023 and completed December 29, 2025, but as of November 2026 no results have been posted on ClinicalTrials.gov or published. Two further phase 2a studies have completed. MK-6024-016 (NCT06482112, 124 adults with MASLD) compared weekly and every-two-week regimens over 28 weeks and posted results on June 1, 2026: relative liver-fat reductions of 67.8% (10 mg weekly), 54.4% (10 mg every two weeks) and 42.1% (15 mg every two weeks), with 5.1% to 9.5% of participants stopping for an adverse event. MK-6024-017 (NCT06465186, 85 adults with compensated MASH cirrhosis, primary endpoint change in liver fat at week 28) completed on August 3, 2026 with results not yet posted. Phase 1 pharmacology studies in hepatic impairment (NCT06052566, 22 participants), otherwise healthy obese adults (NCT06701305) and healthy Chinese volunteers (NCT06836037) round out the registered program.

Merck’s public pipeline chart dated August 5, 2026 lists efinopegdutide in phase 2 for MASH, and no phase 3 trial had been registered on ClinicalTrials.gov as of November 2026. The compound competes with other GLP-1/glucagon dual agonists in the same indication, notably survodutide and pemvidutide, both of which have reported biopsy-based phase 2 histology and moved into phase 3 MASH trials (survodutide’s LIVERAGE program from October 14, 2024; pemvidutide’s phase 3 from July 30, 2026), a step efinopegdutide has not yet taken.

Common dosage forms

• Investigational injection. A solution for subcutaneous injection, supplied only to clinical trial sites.
• Trial presentation. A 20 mg/mL solution in the phase 2a NAFLD study and a 14 mg/mL solution in the phase 1 hepatic-impairment study.
• No approved presentation. No approved product, pen, or commercial presentation exists in any country.

Key considerations

• Regulatory status. The Investigational status reflects an active Merck-sponsored phase 2 program in MASH with no marketing application in any jurisdiction as of November 2026. The phase 2b and cirrhosis studies have completed without reported results.
• Histology gap. Every efficacy result released so far is an imaging endpoint (MRI-PDFF liver fat) or body weight, and the 52-week biopsy-based phase 2b readout that would show whether liver-fat reduction translates into MASH resolution or fibrosis improvement has not been released.
• Gastrointestinal tolerability. Nausea and vomiting were more frequent than with placebo or liraglutide in both Janssen obesity trials, adverse events were reported by 88.9% versus 72.6% of participants in the Merck phase 2a with higher discontinuation for adverse events, and roughly a quarter of participants in the 26-week obesity trial did not complete treatment.
• Not a glucose-lowering drug. Glucagon-receptor activity means it did not lower HbA1c the way pure GLP-1 agonists do and raised fasting glucose in people with type 2 diabetes, and the obesity and diabetes indications were not pursued; it is a liver-targeted candidate.
• Naming confusions. The same molecule appears in the literature under four names (HM12525A or LAPS-GLP/GCG, JNJ-64565111, MK-6024, efinopegdutide), so searches restricted to one code miss earlier or later trials; it is also distinct from Hanmi’s GLP-1/GIP/glucagon triple agonist efocipegtrutide (HM15211).