Efinopegdutide Latest Research: New Indications, Trials & What’s Coming

Introduction

Efinopegdutide’s most important published research is the Romero-Gomez et al. 2023 Journal of Hepatology head-to-head versus semaglutide in MASH patients. That trial established efinopegdutide as a serious MASH candidate with stronger liver fat reduction than semaglutide at the doses tested. Merck is advancing the drug through phase 2b for MASH and has plans for phase 3.

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What Does the Romero-Gomez 2023 Trial Tell Us?

The phase 2a head-to-head trial was a 145-patient randomized study published in Journal of Hepatology in 2023. Patients with biopsy-confirmed MASH or significant hepatic steatosis (MRI-PDFF at least 10%) received efinopegdutide 10 mg weekly, semaglutide 1.0 mg weekly, or placebo for 24 weeks.

Quick Answer: Romero-Gomez 2023 Journal of Hepatology: 72.7% liver fat reduction vs 42.3% for semaglutide at 24 weeks

Key results:

Relative liver fat reduction: 72.7% (efinopegdutide), 42.3% (semaglutide).

Mean weight loss: 8.5% (efinopegdutide), 7.1% (semaglutide).

ALT reduction: about 30 to 40% in efinopegdutide arm.

Tolerability was comparable between the two arms.

This was the first major head-to-head between a dual agonist and a pure GLP-1 agonist specifically for MASH liver fat. The results favored the dual agonist on liver fat, by a wide margin.

What Phase 2b Trials Are Running?

Phase 2b efinopegdutide trials for MASH are ongoing as of 2026. These trials typically extend the duration (52 weeks or more), include biopsy endpoints (MASH resolution, fibrosis improvement), and explore additional dose levels.

Specific trial designs and timelines haven’t all been made public. Merck typically discloses topline results when the data is ready for regulatory submission.

What Is the Phase 3 Outlook?

Phase 3 MASH design probably mirrors what MAESTRO-NASH used for resmetirom (Harrison et al. 2024 NEJM): biopsy at baseline and 52 to 72 weeks, primary endpoints of MASH resolution without worsening fibrosis or fibrosis improvement without worsening MASH.

A phase 3 obesity program is less certain. Merck may pursue obesity as a separate indication or combine MASH and obesity into a single development path. The competitive landscape for obesity is intense, which may affect strategic decisions.

Earliest realistic phase 3 readout is 2027 to 2028. FDA approval could follow in 2028 to 2029.

How Does Efinopegdutide Compare to the Rest of the Pipeline?

The current GLP-1-based pipeline includes several molecules at various stages:

Pemvidutide (Altimmune): dual GLP-1/glucagon. Phase 2b complete. Similar positioning to efinopegdutide.

Survodutide (Boehringer Ingelheim/Zealand): dual GLP-1/glucagon. Phase 3 ongoing.

Retatrutide (Eli Lilly): triple GLP-1/GIP/glucagon. Phase 3 ongoing.

CagriSema (Novo Nordisk): semaglutide plus cagrilintide. Phase 3 complete (REDEFINE 1: 22.7% at 68 weeks).

Orforglipron (Eli Lilly): oral small-molecule GLP-1 agonist. Phase 3 ongoing.

Efinopegdutide’s positioning is strongest in MASH, where the head-to-head data versus semaglutide gives it a clear differentiation story.

What About Alcohol Use Disorder?

Animal studies show GLP-1 receptor agonists may reduce alcohol intake. Whether efinopegdutide specifically pursues alcohol use disorder isn’t confirmed. Class-wide interest in this indication is growing.

What About Cardiovascular Outcomes?

No dedicated cardiovascular outcomes trial has been announced for efinopegdutide. Class effects from semaglutide (SELECT, Lincoff et al. 2023 NEJM) suggest broad benefit; whether efinopegdutide shares those benefits is unstudied.

The glucagon component raises modest concerns about heart rate but the phase 2 signal was small (3 to 5 bpm). A CVOT would be needed for definitive answers.

Are There Pediatric Trials?

No pediatric efinopegdutide trials have been announced. Pediatric development typically follows adult phase 3 by 2 to 3 years.

What’s the Regulatory Timeline?

Realistic timeline:

2026 to 2027: Phase 2b completion and phase 3 initiation.

2027 to 2028: Phase 3 readouts.

2028 to 2029: FDA filing and review.

2029 to 2030: Approval, if all goes well.

Delays are common. Phase 3 enrollment competition with other GLP-1 drugs may slow recruitment. Manufacturing scale-up adds time.

Will Efinopegdutide Be on Shortage Like Semaglutide?

Merck has large manufacturing capacity and a stronger position to avoid shortages than smaller biotechs. But demand for GLP-1 drugs has consistently outpaced supply, so some shortage risk exists.

If shortage occurs, compounded efinopegdutide could become legal. If supply matches demand, compounding won’t happen for efinopegdutide.

What New Science Is Emerging?

Research on dual GLP-1/glucagon agonism continues to refine understanding of optimal receptor activity ratios for different patient populations. Higher glucagon activity may favor MASH and liver disease applications; higher GLP-1 activity favors raw weight loss in patients without significant liver involvement.

Efinopegdutide’s specific receptor ratio hasn’t been publicly disclosed in the same detail as for pemvidutide, but the strong liver fat efficacy suggests meaningful glucagon coverage.

Mechanism studies are also exploring sympathetic nervous system effects, energy expenditure changes, and substrate utilization shifts at individual tissue levels.

What About Combination Therapies?

The pipeline includes many GLP-1-based combinations. Adding amylin agonism (cagrilintide-like compounds) on top of GLP-1/glucagon dual agonism could compound effects.

Whether efinopegdutide will be developed in combination with another agent isn’t public.

What Patient Populations Might Benefit Most?

Based on current data, highest-benefit efinopegdutide candidates appear to be:

Adults with obesity plus MASH or significant hepatic steatosis. Adults with modest T2D plus MASH (because efinopegdutide produces some HbA1c reduction). Adults seeking weight loss with concurrent fatty liver concerns.

For pure obesity without MASH, tirzepatide may produce more weight loss based on SURMOUNT-1 data. For pure CV risk reduction, semaglutide has the strongest evidence base.

How Does TrimRx Position Around Efinopegdutide?

TrimRx currently offers compounded semaglutide and tirzepatide. Efinopegdutide isn’t on the formulary because it isn’t FDA-approved.

When efinopegdutide is approved, TrimRx will evaluate adding it. The free assessment quiz would route patients with significant MASH to efinopegdutide.

What Scientific Questions Remain Open?

Several questions need phase 3 data:

What’s the maximum weight loss ceiling with longer treatment? Does the liver fat advantage hold up against tirzepatide and pemvidutide in head-to-head trials (which may never happen)? Does efinopegdutide reduce major adverse cardiovascular events? Is there fibrosis improvement at 52 to 72 weeks in MASH? What’s the optimal dose for obesity (10 mg may not be the ceiling)?

What Other Research Areas Are Worth Watching?

Efinopegdutide may have applications beyond MASH and obesity:

Type 2 diabetes (modest HbA1c effects suggest some utility but not as a primary diabetes drug).

Chronic kidney disease (class effects from FLOW suggest GLP-1 drugs may benefit CKD; efinopegdutide isn’t studied).

Sleep apnea (tirzepatide gained the SURMOUNT-OSA indication in Dec 2024; efinopegdutide may follow given weight loss).

Heart failure with preserved ejection fraction (STEP-HFpEF showed semaglutide benefit).

Polycystic ovary syndrome.

What Earlier Studies Built the Case for Efinopegdutide?

Phase 1 single-ascending-dose and multiple-ascending-dose studies in healthy volunteers established the pharmacokinetic profile, including the 7 to 10 day half-life and good tolerability at doses up to 10 mg weekly. These studies were conducted by Hanmi initially, then by Merck after licensing.

Phase 1b studies in patients with obesity established initial efficacy signals: meaningful weight loss over 12 weeks even at doses below the eventual phase 2 target.

These early-stage data justified the phase 2 program that produced the MASH head-to-head trial.

Key Takeaway: Phase 2b for MASH ongoing

How Does the Hanmi-Merck Licensing Deal Affect Development?

Hanmi Pharmaceutical originally developed efinopegdutide using its LAPSCOVERY platform. In 2020, Hanmi licensed global development rights (outside Korea) to Merck in a deal worth up to $870 million in milestones plus tiered royalties.

Merck is responsible for clinical development, regulatory filings, and commercialization in all licensed markets. Hanmi retained Korean rights and continues to support development.

This kind of partnership is common in the GLP-1 space. It gives smaller biotechs access to large-pharma development resources while letting them retain regional rights.

What Does the Broader Merck Obesity Strategy Look Like?

Merck has historically focused on cardiovascular, oncology, and infectious disease. Obesity and MASH are newer focus areas. Efinopegdutide is Merck’s main entry in the obesity/MASH space.

Merck’s commercial infrastructure (Januvia for diabetes, Keytruda for cancer) gives it significant ability to scale efinopegdutide if approved. Marketing reach, payer relationships, and physician access are all strengths.

What Competitive Pressures Affect Efinopegdutide’s Path?

The GLP-1 obesity market is dominated by Novo Nordisk (semaglutide) and Eli Lilly (tirzepatide). Combined, these two companies hold over 90% of the current GLP-1 obesity market.

Late-stage challengers include Altimmune (pemvidutide), Boehringer Ingelheim (survodutide), and Lilly itself with retatrutide. Several oral and combination products are also in development.

Efinopegdutide will need a differentiated value proposition to take meaningful market share. The MASH liver fat data is the strongest differentiation story.

What About Real-world Evidence for Efinopegdutide?

Real-world evidence doesn’t exist yet because the drug isn’t approved. Post-approval studies and observational data will accumulate over the first few years after launch.

For GLP-1 drugs that are approved (semaglutide, tirzepatide), real-world evidence has generally confirmed clinical trial efficacy with somewhat reduced effect sizes (typically 70 to 85% of trial averages) due to less structured adherence and follow-up in real-world settings.

What Pharmacovigilance Signals Are Being Watched?

The FDA and EMA monitor several class-wide signals for GLP-1 drugs:

Pancreatitis (longstanding class warning, weak evidence in randomized trials).

Gallbladder disease (modest signal during rapid weight loss).

Thyroid cancer (rodent finding, unclear human relevance, boxed warning).

Aspiration during anesthesia (newer concern with delayed gastric emptying).

Mental health (depression, suicidality; investigation ongoing).

Efinopegdutide’s surveillance will include the same signals plus any drug-specific findings from large phase 3 trials.

What About Manufacturing and Supply Concerns?

Merck has substantial manufacturing capacity for biologic and peptide drugs. The Fc fusion architecture of efinopegdutide is similar to Merck’s other biologic manufacturing experience.

Whether efinopegdutide faces shortages at launch depends on demand. Current GLP-1 drug demand has consistently exceeded supply across the class. If Merck plans conservatively, shortage risk is higher. If they invest heavily in pre-launch manufacturing, supply may be adequate.

How Does This Fit the TrimRx Future Plan?

TrimRx is positioned to evaluate adding new GLP-1 drugs to its formulary as they become approved and clinically relevant. The free assessment quiz and personalized treatment plan can integrate efinopegdutide (and pemvidutide, retatrutide, etc.) into clinical recommendations once they’re available.

For 2026 to 2028, the practical TrimRx GLP-1 options remain compounded semaglutide and tirzepatide. Approved options will expand over the rest of the decade as pipeline drugs reach market.

What About Long-term Outcomes Data?

Long-term outcomes (cardiovascular events, kidney events, mortality) require trials lasting 3 to 5 years. No long-term outcomes data exists for efinopegdutide. Class effects from semaglutide (SELECT, FLOW) suggest benefit but direct evidence for efinopegdutide is years away.

How Does Efinopegdutide Compare for Sleep Apnea?

No specific OSA trial has been run for efinopegdutide. Tirzepatide gained the SURMOUNT-OSA indication in December 2024 based on direct OSA trial data. Efinopegdutide would need its own OSA trial for that indication.

Weight loss alone improves OSA in many patients regardless of which drug drives the loss.

What About Heart Failure with Preserved Ejection Fraction?

The STEP-HFpEF trial showed semaglutide improved symptoms and exercise capacity in patients with HFpEF and obesity. Whether efinopegdutide will pursue this indication isn’t public.

The dual GLP-1/glucagon mechanism could plausibly produce similar or better benefits given the broader metabolic effects, but trial data would be needed.

What About Kidney Outcomes?

The FLOW trial (Perkovic et al. 2024 NEJM) showed semaglutide reduced kidney and CV death by 24% in patients with diabetes and CKD. Whether efinopegdutide shares this benefit hasn’t been studied directly.

Kidney protection is increasingly recognized as a class effect of GLP-1 drugs. The glucagon component in efinopegdutide may or may not preserve this benefit.

What New Mechanisms Are Being Explored?

Beyond dual and triple agonism at GLP-1/GIP/glucagon, research is exploring:

Amylin agonists (cagrilintide-class).

PYY analogs (peptide YY, another gut hormone).

Oxyntomodulin analogs (natural dual GLP-1/glucagon).

GIP antagonists (Amgen’s MariTide).

Combination products (CagriSema is the first).

Efinopegdutide may eventually be combined with one of these mechanisms.

How Does the Research Landscape Affect TrimRx Planning?

TrimRx tracks the GLP-1 pipeline closely. New approvals are evaluated for clinical fit, cost-effectiveness, and patient demand. The platform’s free assessment quiz and personalized treatment plan can incorporate new drugs as they become available.

For 2026 to 2028, the practical TrimRx GLP-1 options remain compounded semaglutide and tirzepatide. New approved options will expand the formulary over the rest of the decade.

What Investor and Market Signals Matter?

Merck’s commitment to efinopegdutide development is the strongest signal for the drug’s commercial viability. Phase 3 trial commitment, manufacturing investment, and marketing infrastructure all indicate Merck’s seriousness about the program.

Conference presentations, peer-reviewed publications, and SEC filings (Merck’s 10-K and 10-Q reports) provide updates on development progress.

Bottom line: Originally developed by Hanmi Pharmaceutical, licensed to Merck for global rights outside Korea

FAQ

When Will Efinopegdutide Be Approved?

Earliest realistic FDA approval is 2028 to 2029.

What’s the Most Important Finding From Phase 2?

The Romero-Gomez 2023 head-to-head data: 72.7% liver fat reduction at 24 weeks vs 42.3% for semaglutide. That’s the basis for efinopegdutide’s MASH positioning.

Will Efinopegdutide Work for Diabetes?

Modest HbA1c effects suggest some utility but not as a primary diabetes drug. Use semaglutide or tirzepatide for primary diabetes management.

Is Efinopegdutide Better Than Pemvidutide?

Both are dual GLP-1/glucagon agonists with similar positioning. Efinopegdutide has slightly larger liver fat effects in available data; pemvidutide may have better lean mass preservation. Direct head-to-head doesn’t exist.

What About Long-term Safety?

Long-term efinopegdutide safety data doesn’t exist yet. Phase 3 trials will accumulate longer follow-up.

When Might I See Efinopegdutide at TrimRx?

After FDA approval and TrimRx evaluation, which puts the earliest availability around 2029 or later.

Will Efinopegdutide Be Cheaper or More Expensive Than Current Options?

Likely priced similar to current brand GLP-1 drugs at launch. Compounded equivalents probably won’t exist for at least a year or two after launch.

Is There a Head-to-head Trial Against Tirzepatide?

Not published. The only head-to-head efinopegdutide trial against another active drug is the Romero-Gomez 2023 study against semaglutide.

What Does the Phase 2b Efinopegdutide Trial Test?

The active phase 2b MASH trial extends the 24-week phase 2a design to longer duration with biopsy endpoints. Specific design details are limited in public disclosures.

Will Efinopegdutide Be Useful for Older Adults?

The Fc fusion architecture extends half-life predictably across patient populations including older adults. Phase 3 trials will include older subjects to confirm safety and efficacy.

What Clinical Trials Are Recruiting Now?

Search clinicaltrials.gov for “efinopegdutide” or “MK-6024” to find currently recruiting studies. Eligibility varies; common requirements include specific BMI ranges and MASH-related criteria for MASH trials.

How Does Hanmi’s Korean Development Progress Affect Global Timeline?

Hanmi retains Korean rights and is developing the drug separately for that market. Korean regulatory approvals may come before US approval depending on local trial timing.

Disclaimer: This content is for informational purposes only and does not constitute medical advice. It is not intended to diagnose, treat, cure, or prevent any disease or condition. Individual results may vary. Always consult a qualified healthcare professional before starting any weight loss program or medication.