Efinopegdutide (MK-6024) is an investigational once-weekly injectable peptide that activates both the GLP-1 receptor and the glucagon receptor. Merck develops it for MASH, the inflammatory form of fatty liver disease, under license from Hanmi Pharmaceutical. In a 24-week head-to-head trial it cut liver fat by 72.7% vs 42.3% with semaglutide 1 mg, and in November 2026 Merck reported that its 52-week phase 2b biopsy trial met its main goal.
The single most important fact: efinopegdutide is not approved anywhere. The FDA granted it Fast Track designation for NASH (the older name for MASH) in 2023 (Merck, June 2023), which speeds up FDA interactions but is not an approval. No phase 3 trial was registered on ClinicalTrials.gov when we checked on November 7, 2026.
This page summarizes the published trials, registry results and the latest conference reports, with notes for anabolics.app readers on liver fat, lean mass, lipids and sport. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Dual GLP-1 and glucagon receptor agonist (co-agonist); long-acting peptide |
| Developer / codes | Hanmi Pharmaceutical (HM12525A); Janssen (JNJ-64565111); Merck (MK-6024) since 2020 |
| Approval status | Investigational; not approved by the FDA, EMA or any other regulator |
| Route | Subcutaneous injection once weekly |
| Doses studied | MASH phase 2b: 4, 7 or 10 mg/week after escalation from 2 mg; earlier obesity trials: 5.0, 7.4 and 10.0 mg/week |
| Half-life | Designed for weekly dosing; a human half-life is not reported in the sources we reviewed |
| US regulatory designation | Fast Track for NASH (disclosed June 2023) |
| Current status | Phase 2b MASH trial completed December 2025, results released as an AASLD abstract in November 2026; cirrhosis phase 2a completed August 2026 |
| WADA status | Not named on the 2026 List; as an unapproved drug it falls under S0 (non-approved substances) |
What it is
Efinopegdutide is a weekly peptide that acts on two receptors:
- GLP-1 receptor. This is the target of semaglutide. It lowers appetite and food intake and improves blood sugar control.
- Glucagon receptor. Glucagon receptors are concentrated in the liver. Activating them raises fat burning in liver cells and lowers new fat production, so they can reduce liver fat directly as well as through weight loss (Romero-Gómez et al., J Hepatol 2023).
That liver action is why Merck develops it for liver disease rather than obesity.
Three owners, three codes
Hanmi Pharmaceutical discovered the molecule as HM12525A. Janssen ran phase 2 obesity trials under the code JNJ-64565111 in 2018–2019 (NCT03486392). On August 4, 2020, Merck licensed exclusive worldwide rights from Hanmi for $10 million upfront and up to $860 million in milestones, plus royalties; Hanmi kept an option to sell the drug in Korea (Merck and Hanmi, August 2020).
How it compares with related drugs
| Drug | Receptors activated | Status (November 2026) | Library page |
|---|---|---|---|
| Semaglutide | GLP-1 | Approved, including for MASH with fibrosis (accelerated approval) | Semaglutide |
| Tirzepatide | GIP and GLP-1 | Approved | Tirzepatide |
| Efinopegdutide | GLP-1 and glucagon | Phase 2b complete (MASH) | This page |
| Pemvidutide | GLP-1 and glucagon | Phase 3 (MASH) | Pemvidutide |
| Survodutide | GLP-1 and glucagon | Investigational | Survodutide |
| Mazdutide | GLP-1 and glucagon | Approved in China | Mazdutide |
| Retatrutide | GIP, GLP-1 and glucagon | Investigational | Retatrutide |
Pemvidutide and survodutide are the nearest competitors in MASH. A 2026 meta-analysis of 19 trials of GLP-1/glucagon dual agonists in overweight and obesity found meaningful weight loss and metabolic improvements, more adverse events of any kind than controls, but no increase in serious adverse events (Amjad et al., Diabetes Obes Metab 2026).
Pharmacokinetics
Detailed human pharmacokinetic values are not published in the sources we found. Merck has completed phase 1 studies in healthy adults with obesity, in healthy Chinese volunteers and in people with hepatic impairment (NCT06701305; NCT06052566), but their results are not posted.
One practical finding concerns dosing frequency. A phase 2a study randomized 124 adults with fatty liver disease to 10 mg weekly, 10 mg every two weeks or 15 mg every two weeks for 28 weeks (NCT06482112):
| Outcome at week 28 | 10 mg weekly | 10 mg every 2 weeks | 15 mg every 2 weeks |
|---|---|---|---|
| Relative reduction in liver fat | 67.8% | 54.4% | 42.1% |
| Body weight change | −7.5% | −3.9% | −4.1% |
| Any adverse event | 83.3% | 82.1% | 85.7% |
| Stopped for adverse events | 7.1% | 5.1% | 9.5% |
Weekly dosing worked best. The study had no placebo arm and was open label.
Regulatory status
- Not approved. No regulator has approved efinopegdutide.
- Fast Track. Merck disclosed FDA Fast Track designation for NASH in June 2023 (Merck, June 2023).
- Pipeline position. Merck’s third-quarter 2026 earnings presentation lists efinopegdutide (MK-6024) for MASH and named presentation of the phase 2b results at AASLD as an upcoming milestone (Merck 3Q 2026 presentation).
- No phase 3 yet. We found no phase 3 trial on ClinicalTrials.gov as of November 7, 2026.
- Obesity and diabetes. Janssen’s obesity and diabetes trials were completed in 2019; Merck develops the drug only for liver disease.
What the research shows
Liver fat vs semaglutide (phase 2a)
This open-label trial randomized 145 adults with fatty liver disease (at least 10% liver fat on MRI-PDFF, an MRI method that measures liver fat) to efinopegdutide 10 mg or semaglutide 1 mg weekly for 24 weeks. Both were stepped up over 8 weeks. Mean BMI was 34.3, mean liver fat 20.3%, and a third had type 2 diabetes (Romero-Gómez et al., J Hepatol 2023; NCT04944992 results).
| Outcome at week 24 | Efinopegdutide 10 mg (n = 72) | Semaglutide 1 mg (n = 73) |
|---|---|---|
| Relative reduction in liver fat (primary) | 72.7% | 42.3% (p under 0.001) |
| Absolute reduction in liver fat (percentage points) | 14.9 | 8.8 |
| Body weight change | −8.5% | −7.1% (p = 0.085, not significant) |
| Triglycerides | −30.9% | −23.3% |
| LDL cholesterol | −13.0% | −6.9% |
| ApoB | −14.7% | −9.2% |
| HDL cholesterol | −8.1% | +3.6% |
Efinopegdutide removed much more liver fat for a similar amount of weight loss, which fits the idea that the glucagon component acts on the liver directly. Two limits apply: semaglutide was given at its 1 mg diabetes dose, not the 2.4 mg dose used for obesity and MASH, and liver fat on MRI is a surrogate marker, not the biopsy outcome regulators require.
A note on lipids. Efinopegdutide lowered LDL, apoB and triglycerides more than semaglutide, but it also lowered HDL by 8.1%, while semaglutide raised it slightly. Anyone already tracking a low HDL should know about that difference.
MASH with fibrosis (phase 2b, 52 weeks)
The phase 2b trial (NCT05877547) enrolled 381 adults with biopsy-confirmed MASH and moderate to advanced (F2–F3) fibrosis. They were randomized to efinopegdutide 4, 7 or 10 mg, placebo, or open-label semaglutide 2.4 mg, all weekly for 52 weeks. The registry lists it as completed on December 29, 2025.
Results were released as an abstract at the AASLD Liver Meeting (November 5–9, 2026) and reported by trade and Korean news outlets on November 5–6, 2026 (Endpoints News; The Bio News; Medicopharma). Merck had not posted results on ClinicalTrials.gov, and we did not find a Merck press release or a peer-reviewed paper. The figures below are as reported from the abstract:
| Outcome at week 52 | Placebo | 4 mg | 7 mg | 10 mg | Semaglutide 2.4 mg |
|---|---|---|---|---|---|
| MASH resolution without fibrosis worsening (primary) | 13% | 56% | 63% | 61% | 53% |
| Fibrosis improved ≥1 stage without MASH worsening | 21% | 43% (p = 0.004) | 52% (p under 0.001) | 34% (p = 0.072, not significant) | 25% |
| Stopped for adverse events | about 1% | 3–4% | 3–4% | 11% | about 1% |
All three doses beat placebo on the primary endpoint (p under 0.001). The 7 mg dose looked best overall, with the largest fibrosis effect and a low dropout rate. Numerically, 7 mg was ahead of semaglutide 2.4 mg on both measures, but no statistical comparison with semaglutide was reported, and the semaglutide arm was not blinded. Weight-loss and liver-fat results from this trial were not in the reports we could access.
For context, semaglutide 2.4 mg in its own phase 3 MASH trial (ESSENCE) resolved steatohepatitis in 62.9% vs 34.3% on placebo and improved fibrosis in 36.8% vs 22.4% at 72 weeks (Sanyal et al., NEJM 2025). Different trials have different placebo rates, so cross-trial comparisons are unreliable.
Cirrhosis (phase 2a)
A 28-week trial in 85 adults with compensated cirrhosis from MASH, comparing efinopegdutide with placebo and measuring liver fat, completed on August 3, 2026 (NCT06465186). No results were posted when we checked.
Obesity (Janssen trials, as JNJ-64565111)
Before Merck’s MASH program, Janssen tested the same molecule for weight loss, with no dose escalation:
- Without diabetes. 474 adults with a BMI of 35–50 received 5.0, 7.4 or 10.0 mg weekly, placebo, or open-label liraglutide 3.0 mg daily for 26 weeks. Placebo-adjusted weight loss was 6.8%, 8.1% and 10.0%, vs 5.8% for liraglutide. Only 72.4% completed treatment (Alba et al., Clin Obes 2021).
- With type 2 diabetes. In 195 adults over 12 weeks, placebo-adjusted weight loss was 4.6–7.2%, but HbA1c did not improve, and fasting glucose and insulin rose numerically (Di Prospero et al., Clin Obes 2021). Glucagon raises blood sugar, and in this trial that effect offset the GLP-1 component.
Lean mass and body composition
No efinopegdutide trial has reported lean mass or muscle outcomes. The MASH trials measure liver biopsy, liver fat and body weight, not DXA body composition. Claims that glucagon co-agonists spare muscle remain unproven for this drug. For the GLP-1 class generally, a 2026 meta-analysis of semaglutide trials estimated that about 35% of the weight lost was lean mass (Eisa and Barood, Diabetes Obes Metab 2026).
Liver fat is not the same as steroid-related liver strain
Readers who use anabolic-androgenic steroids (AAS) may wonder whether a “liver drug” protects the liver. The evidence does not support that idea:
- Efinopegdutide was tested for fat in the liver caused by metabolic disease (MASLD and MASH). Steroid-related liver injury is a different problem, typically cholestasis (impaired bile flow), peliosis hepatis or tumors (Petrovic et al., World J Gastroenterol 2022). No trial has tested efinopegdutide for drug-induced liver injury.
- An MRI study found that bodybuilders using performance-enhancing drugs had larger livers (2.57 L) than natural bodybuilders (1.82 L) or controls (1.79 L), along with larger hearts and other organs (Fuchs et al., Med Sci Sports Exerc 2026). That study measured organ volume, not fat, and says nothing about efinopegdutide.
- In Janssen’s obesity trial, “hepatic enzyme increased” was reported in 6 of 118 people on 10 mg and 2 of 118 on 7.4 mg vs none on placebo (NCT03486392 results). Those doses were started without escalation.
No study has enrolled people on testosterone or other AAS, so how these drugs interact is unknown. The TUDCA and ursodiol pages cover the separate evidence on bile-acid drugs.
Side effects and risks
Gastrointestinal effects
In the head-to-head trial, adverse events of any kind occurred in 88.9% on efinopegdutide vs 72.6% on semaglutide, mostly because of stomach and gut effects. 5.6% stopped efinopegdutide for adverse events vs none on semaglutide (NCT04944992 results):
| Adverse event (24 weeks) | Efinopegdutide 10 mg (n = 72) | Semaglutide 1 mg (n = 73) |
|---|---|---|
| Nausea | 27.8% | 31.5% |
| Constipation | 16.7% | 5.5% |
| Diarrhea | 16.7% | 17.8% |
| Vomiting | 16.7% | 15.1% |
| Decreased appetite | 16.7% | 15.1% |
| Abdominal pain | 12.5% | 2.7% |
| Upper abdominal pain | 9.7% | 1.4% |
Without dose escalation, tolerability was much worse. In Janssen’s obesity trial, nausea affected 51–68% and vomiting 20–54% across the three doses, vs 7% and 0% on placebo and 40% and 17% on liraglutide (NCT03486392 results). In the phase 2b MASH trial, the 10 mg dose had the most gastrointestinal events and an 11% dropout rate (The Bio News).
Blood sugar
Glucagon raises blood sugar. In people with type 2 diabetes, the Janssen trial found no HbA1c improvement and numerical rises in fasting glucose and insulin (Di Prospero et al. 2021). The later Merck trials used gradual escalation. Glucose effects in people with diabetes on those regimens are not reported in the trial summaries we reviewed.
Serious adverse events and gaps
Serious adverse events were uncommon in the head-to-head trial (1 of 72 on efinopegdutide, a urinary stone, and 1 of 73 on semaglutide). In the dosing-frequency study, serious events included one supraventricular tachycardia (a fast heart rhythm) and one cholecystitis (gallbladder inflammation) on 15 mg every two weeks (NCT06482112 results). Full safety data from the 381-person phase 2b trial have not been published. Heart rate, gallbladder and pancreas effects, effects in cirrhosis, and long-term safety are not yet well characterized.
Use in sport
Efinopegdutide is not named on the WADA Prohibited List. Section S0 prohibits at all times any pharmacological substance not addressed elsewhere on the List that has no current approval by any government health authority for human therapeutic use, including drugs “under pre-clinical or clinical development” (WADA 2026 Prohibited List). As an unapproved drug, efinopegdutide falls under S0. It is available only inside Merck’s clinical trials, so anything sold online under this name is unverified.
Key takeaways
- A weekly GLP-1 and glucagon dual agonist aimed at the liver. Merck develops efinopegdutide (MK-6024) for MASH under license from Hanmi.
- Not approved anywhere. It has FDA Fast Track designation, and no phase 3 trial was registered as of November 7, 2026.
- Strong liver-fat effect. It cut liver fat by 72.7% vs 42.3% with semaglutide 1 mg at 24 weeks, with similar weight loss.
- Phase 2b met its goal. As reported from the AASLD 2026 abstract, MASH resolved in 56–63% vs 13% on placebo at 52 weeks; 7 mg also improved fibrosis (52% vs 21%). A peer-reviewed paper has not appeared.
- Not a muscle or “liver support” drug. No trial has measured lean mass, and none has tested it for steroid-related liver injury. It lowered HDL by 8.1% in the head-to-head trial.
- Prohibited in sport under S0. As an unapproved drug it falls under WADA’s non-approved substances class.
Sources
- Romero-Gómez M, Lawitz E, Shankar RR, et al. 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. 2023;79(4):888–897. PubMed.
- ClinicalTrials.gov. A study of efinopegdutide (MK-6024) in participants with nonalcoholic fatty liver disease (NAFLD) (MK-6024-001). NCT04944992, results posted November 15, 2023. ClinicalTrials.gov.
- ClinicalTrials.gov. A clinical study of efinopegdutide in participants with precirrhotic nonalcoholic steatohepatitis (NASH) (MK-6024-013). NCT05877547. ClinicalTrials.gov.
- ClinicalTrials.gov. Alternate dosing study of MK-6024 in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) (MK-6024-016). NCT06482112, results posted June 1, 2026. ClinicalTrials.gov.
- ClinicalTrials.gov. A clinical study of efinopegdutide in people with compensated cirrhosis due to steatohepatitis (MK-6024-017). NCT06465186. ClinicalTrials.gov.
- ClinicalTrials.gov. Phase 1 studies of efinopegdutide in healthy obese participants (MK-6024-015) and in hepatic impairment (MK-6024-014). NCT06701305, NCT06052566. NCT06701305; NCT06052566.
- ClinicalTrials.gov. A study to evaluate the safety and efficacy of JNJ-64565111 in non-diabetic severely obese participants. NCT03486392, results posted February 5, 2020. ClinicalTrials.gov.
- Alba M, Yee J, Frustaci ME, et al. 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. 2021;11(2):e12432. PubMed.
- Di Prospero NA, Yee J, Frustaci ME, et al. 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. 2021;11(2):e12433. PubMed.
- Merck. Merck and Hanmi Pharmaceutical enter into licensing agreement to develop efinopegdutide, an investigational once-weekly therapy for nonalcoholic steatohepatitis (NASH). Press release, August 4, 2020. Merck.
- Merck. Merck to present data for efinopegdutide (MK-6024), an investigational GLP-1/glucagon receptor co-agonist, in patients with nonalcoholic fatty liver disease (NAFLD) at EASL 2023. Press release, June 12, 2023. Merck.
- Merck. Third-quarter 2026 sales and earnings presentation. October 2026. Merck.
- Endpoints News. #AASLD26: Merck unwraps biopsy data for MASH drug it got from South Korea’s Hanmi. November 5, 2026. Endpoints News.
- The Bio News. MSD and Hanmi efinopegdutide phase 2b results: MASH resolution 63%, fibrosis improvement 52% (in Korean). November 6, 2026. The Bio News; Medicopharma. [AASLD 2026] Hanmi’s MASH drug improves liver fibrosis at 52 weeks (in Korean). November 6, 2026. Medicopharma.
- Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. N Engl J Med. 2025;392(21):2089–2099. PubMed.
- Amjad MM, Khan MM, Sarwar F, et al. Efficacy and safety of dual GLP-1/glucagon receptor agonism in overweight and obesity: a class-specific systematic review and meta-analysis. Diabetes Obes Metab. 2026;28(12):11872–11890. PubMed.
- Eisa N, Barood O. Lean mass changes with incretin therapy versus lifestyle intervention: a systematic review and meta-analysis of randomised controlled trials. Diabetes Obes Metab. 2026;28(6):4818–4827. PubMed.
- Petrovic A, Vukadin S, Sikora R, et al. Anabolic androgenic steroid-induced liver injury: an update. World J Gastroenterol. 2022;28(26):3071–3080. PubMed.
- Fuchs CJ, Brauwers B, Trommelen J, et al. When size goes inside: visceromegaly in bodybuilders is not attributed to high-protein intake but more likely associated with the use of appearance- and performance-enhancing drugs. Med Sci Sports Exerc. 2026;58(9):1878–1890. PubMed.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.