Pemvidutide

At a glance

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What is pemvidutide?

Pemvidutide (development code ALT-801) is a synthetic peptide that activates two metabolic-hormone receptors at once: GLP-1 (glucagon-like peptide-1) and glucagon.^[8] What makes it distinctive is that it engages those two receptors in a balanced 1:1 ratio — the design hypothesis being that an even split maximizes weight loss and the direct liver benefits of glucagon while limiting the gastrointestinal intolerance that comes from leaning too hard on GLP-1.

It is being developed by Altimmune, a clinical-stage company in Gaithersburg, Maryland, primarily for MASH (metabolic dysfunction-associated steatohepatitis — fatty-liver disease that has progressed to inflammation and scarring), as well as obesity, alcohol use disorder, and alcohol-associated liver disease. The molecule incorporates a proprietary "EuPort" domain — a glycolipid/surfactant attachment that binds albumin and slows release, enabling once-weekly dosing without the gradual dose escalation that most incretin drugs require.^[8]

Unlike a pure GLP-1 drug such as semaglutide, pemvidutide adds glucagon receptor agonism. Glucagon acts directly on the liver to burn fat and increases whole-body energy expenditure — which is why dual agonists like pemvidutide and survodutide have drawn so much attention specifically for liver disease.

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How it works

In plain terms, pemvidutide mimics two hormones your body uses to manage appetite, blood sugar, and energy balance. The GLP-1 arm reduces appetite and helps regulate glucose; the glucagon arm tells the liver to break down stored fat and nudges the body to burn more energy. Together they are meant to reproduce the complementary effects of diet (eating less) and exercise (burning more).^[7]

The "balanced 1:1" framing matters. Earlier dual agonists tended to favor one receptor over the other. Pemvidutide was deliberately tuned to a roughly even split, on the theory that this produces stronger weight loss and better metabolic control than a design biased toward either hormone.

Detailed mechanism (for advanced readers)

Pemvidutide is a balanced (1:1) GLP-1 / glucagon receptor dual agonist:^[8]

GLP-1 receptor agonism:

• Glucose-dependent insulin secretion from pancreatic beta cells
• Central appetite suppression via hypothalamic and brainstem GLP-1 receptors
• Delayed gastric emptying (contributes to satiety and to GI side effects)
• Drives the appetite/weight side of the "diet" analogy

Glucagon receptor agonism (the differentiator vs. pure GLP-1 drugs):

• Acts directly on the liver to promote hepatic lipid oxidation, reducing liver fat
• Increases whole-body energy expenditure (the "exercise" analogy)
• Associated in preclinical work with reductions in hepatic inflammation and fibrosis
• This is the component shared with survodutide and retatrutide, and absent from semaglutide and tirzepatide

Why "balanced" matters: Glucagon agonism alone can raise blood glucose; the GLP-1 arm offsets that, while glucagon adds energy expenditure and direct liver effects. Tuning the two to roughly 1:1 is intended to capture the upside of each while keeping glucose control intact.

The EuPort domain and dosing:

• A proprietary glycolipid/surfactant moiety conjugated to the peptide
• Provides near-quantitative but transient binding to serum albumin (estimated >99%), protecting the peptide from proteolysis and renal clearance
• Surfactant-like properties form micelles that slow entry into the bloodstream
• Net result: a serum half-life long enough for once-weekly dosing without dose titration

A note on identity: The full amino acid sequence of pemvidutide has not been publicly disclosed by Altimmune. Public chemistry databases list a molecular formula of C₁₈₂H₂₇₅N₃₉O₅₄ and a molecular weight of approximately 3,873 Da. We report what is disclosed and flag the rest as unknown rather than estimate it.

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What the research says

Pemvidutide's liver and metabolic data are genuinely promising — and the FDA's Breakthrough Therapy Designation reflects that. The registrational Phase 3 has now started, which is a real milestone. But the evidence base is still Phase 2b: the IMPACT trial met one of its two co-primary endpoints at 24 weeks and missed the other, the Phase 3 result is four years out, and there is no long-term safety data. Encouraging is not the same as proven.

Research timeline

Pemvidutide has moved steadily from preclinical work into Phase 3:

Human clinical trials

Pemvidutide has been studied across four completed human programs with a combined enrollment of roughly 800 participants:

Phase 1b MASLD (Harrison 2025): A 12-week study (n=94) that first showed the hepatic effect — up to a 68.5% reduction in liver fat at 1.8 mg.^[5]

Phase 2 MOMENTUM obesity (2023): A 48-week trial (n=391) establishing weight-loss efficacy and a favorable lean-mass-preservation profile.^[6]

Phase 2b IMPACT MASH (2026): The pivotal trial in biopsy-confirmed F2/F3 MASH (n=212), randomized 1:2:2 to placebo, 1.2 mg, or 1.8 mg weekly for 48 weeks. The 24-week results are peer-reviewed in The Lancet; the 48-week data were presented at EASL 2026.^[1][2]

Phase 2 RECLAIM, alcohol use disorder (2026): A 24-week trial (n=100) of pemvidutide 2.4 mg vs. placebo in adults with moderate-to-severe alcohol use disorder, reported as topline in July 2026.^[12]

A second indication: alcohol use disorder

This one is worth pausing on, because it is a genuinely different use than the rest of pemvidutide's program. There has been growing interest in whether GLP-1-based drugs reduce drinking, mostly from observational data and small studies. RECLAIM is one of the first randomized, placebo-controlled trials in this class designed specifically to answer it.^[12]

The result was positive: participants on pemvidutide cut about 1.45 more heavy drinking days per week than those on placebo, and the supporting endpoints — including a blood biomarker that does not depend on self-reporting — moved in the same direction. Altimmune has asked the FDA for an end-of-Phase-2 meeting.

The limits matter just as much. This was 100 people, 50 per arm, over 24 weeks, and the results exist only as a company press release — no publication, no conference presentation, no independent review of the data. And the drug was harder to tolerate here than in the liver trials, where the doses are lower: one in ten participants stopped because of drug-related side effects, compared with none on placebo. A promising signal in a condition with few effective medications is worth taking seriously. It is not yet a treatment.

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What the evidence shows

Pemvidutide has generated real excitement for liver disease specifically. Here's what the published and presented research actually supports:

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Safety & side effects

What clinical trials show

Pemvidutide's safety profile is based on roughly 700 participants across Phase 1b, Phase 2, and Phase 2b trials. Across these studies, tolerability has been a relative strength for the program.

Gastrointestinal events (the most common side effects): As with the GLP-1 class, the dominant side effects are gastrointestinal. In IMPACT, GI adverse events were predominantly mild-to-moderate and concentrated in the first roughly 8 weeks of treatment.^[2] A design goal of the balanced 1:1 ratio — and of starting at a therapeutic dose without titration — was to keep GI intolerance manageable.

Tolerability and discontinuation: At 48 weeks in IMPACT, treatment discontinuation due to adverse events was approximately 1% — a notably low figure, and one the company has highlighted as a differentiator.^[2] In the MOMENTUM obesity trial, the company reported no imbalances in cardiac events or arrhythmias and no clinically meaningful increase in heart rate.^[6]

Other safety considerations

• Glucagon-specific effects: Adding glucagon agonism is the novel element. Glucagon can raise blood glucose and heart rate; the balanced design is intended to offset the glucose effect with the GLP-1 arm. Long-term effects of chronic glucagon receptor stimulation are not yet characterized in humans.
• Lean mass loss: Expected with weight loss, but the reported ratio (only ~21.9% of weight lost from lean mass in MOMENTUM) is more favorable than typically reported for incretin drugs.
• Unknown long-term safety: The longest trials run 48 weeks. There is no multi-year data and no post-marketing surveillance, because the drug is not approved.
• Class-level warnings: GLP-1 receptor agonists carry warnings including a thyroid C-cell tumor concern (from rodent studies) and pancreatitis. Pemvidutide's specific risk has not been characterized in humans.

What we don't know about safety

There are important gaps in the pemvidutide safety data:

• No long-term (>48 week) data: Chronic-use safety is unknown.
• No post-marketing surveillance: All data comes from controlled clinical trials. Real-world patterns may differ.
• Glucagon receptor uncertainty: The long-term metabolic consequences of chronic glucagon receptor agonism — on hepatic glucose production, bone, and other systems — are not well understood.
• No thyroid C-cell or pancreatitis characterization in humans: These are class-level concerns that have not been specifically ruled in or out for pemvidutide.
• No pregnancy or drug-interaction data published.
• 48-week IMPACT data not yet peer-reviewed: The most complete dataset to date comes from a conference presentation and company release.
• Tolerability is dose-dependent, and the higher dose is harder: The ~1% discontinuation figure comes from the MASH trials, which use 1.2 and 1.8 mg. At 2.4 mg in the RECLAIM alcohol-use-disorder trial, 10% of participants stopped because of drug-related side effects and nausea affected 44%. The favorable tolerability story should not be generalized across doses.

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Legal & regulatory status

As of August 2026:

FDA status

Pemvidutide is not FDA-approved for any indication. It is an investigational drug that entered Phase 3 development for MASH in August 2026.

• Breakthrough Therapy Designation (MASH): Granted January 5, 2026, based on 24-week IMPACT data. This designation expedites FDA development and review for serious conditions where early data suggest substantial improvement over existing options. It is a development status, not an approval — pemvidutide cannot be prescribed on the basis of this designation.^[4]
• Fast Track designations: Granted for both MASH and alcohol use disorder — again, expedited-development statuses, not approvals.
• No approved pemvidutide product exists. It is not a component of any FDA-approved drug and has not been found safe and effective for any condition.^[10]
• Phase 3 has begun. Altimmune initiated PERFORMA on August 3, 2026 — the registrational trial in MASH with moderate-to-advanced (F2-F3) fibrosis. It enrolls roughly 1,790 participants across two cohorts: about 990 assessed by liver biopsy, supporting a potential accelerated approval, and about 800 assessed by non-invasive tests. Doses are 1.2, 1.8, and 2.4 mg. The 52-week primary readout is expected in 2029, with a roughly 60-month liver-outcomes endpoint supporting full approval after that.^[11] Starting a Phase 3 is a meaningful step, but it is the beginning of the pivotal evidence, not the end.

Other programs in development

• RECLAIM (alcohol use disorder): Reported positive topline results on July 28, 2026. Altimmune has requested an end-of-Phase-2 meeting with the FDA and says European regulatory engagement is underway.^[12]
• RESTORE (alcohol-associated liver disease): Completed enrollment in July 2026 (approximately 120 participants, 48 weeks). Topline is expected in the second half of 2027.^[13]
• Obesity: There has been no update to a standalone obesity program. The Phase 2 MOMENTUM trial remains the most recent obesity data, and Altimmune's lead indication is liver disease, not weight loss — a distinction worth keeping in mind if you encounter pemvidutide described as an obesity drug.^[13]

How to access pemvidutide today

The only legal way to access pemvidutide is through enrollment in a clinical trial. Trial listings can be found at ClinicalTrials.gov by searching "pemvidutide" or "ALT-801."

WADA / USADA status

Pemvidutide is not prohibited under the 2026 WADA Prohibited List. GLP-1 receptor agonists are on WADA's Monitoring Program rather than the Prohibited List, so their use by athletes is tracked but does not constitute an anti-doping violation. As a glucagon/GLP-1 dual agonist, pemvidutide is not currently prohibited, though WADA could reclassify the GLP-1 class in a future update.^[9]

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How pemvidutide compares

Pemvidutide's natural comparators are other glucagon-containing agonists in metabolic and liver development — especially survodutide (a GLP-1/glucagon dual agonist from Boehringer Ingelheim) and retatrutide (a triple GIP/GLP-1/glucagon agonist from Eli Lilly). No head-to-head trials exist, so the comparison below relies on cross-trial data, which has important limitations:

The key tradeoffs:

• Weight loss: Pemvidutide's peak obesity weight loss (~15.6%) is meaningful but lower than retatrutide's cross-trial figures (24-29%) and somewhat below survodutide's reported range. All three lack head-to-head data.^[6]
• Liver focus: Pemvidutide's lead indication is MASH, where its glucagon-driven liver-fat reduction (up to 68.5%) and Breakthrough Therapy Designation are the headline. Survodutide is also strongly positioned in MASH.^[5]
• Lean mass: Pemvidutide's reported lean-mass-preservation profile (only ~21.9% of weight lost from lean mass) is a distinguishing claim worth watching as larger datasets accrue.
• Development stage: All three are now in Phase 3, but pemvidutide entered most recently (PERFORMA started August 2026, reading out in 2029) and has the least accumulated late-stage evidence.
• Availability: None of the three is FDA-approved. All are trial-only and cannot be compounded.

The bottom line: pemvidutide is a promising contender whose strongest case is in liver disease, where the glucagon arm and a favorable tolerability profile stand out. It has just started its pivotal trial, so its data is not yet confirmed by Phase 3 — and a positive alcohol-use-disorder result has opened a second direction that nobody was writing about a year ago.

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Related content

Peptide

Survodutide Profile

Boehringer Ingelheim's GLP-1/glucagon dual agonist, also in MASH development. The closest mechanistic comparator to pemvidutide.

Peptide

Retatrutide Profile

Eli Lilly's triple GIP/GLP-1/glucagon agonist. Shares the glucagon arm that drives pemvidutide's liver-fat effects, with a third receptor added.

Peptide

Cagrilintide Profile

A long-acting amylin analog in metabolic development. Useful contrast: a different (amylin) mechanism for weight and metabolic control.

Guide

What Are Peptides?

A foundational primer — helpful context for understanding pemvidutide's dual-agonist mechanism.

Guide

Peptide vs. Small Molecule vs. Biologic

Where peptide drugs like pemvidutide sit relative to small molecules and biologics — and why that shapes how they are dosed and regulated.

Tool

Peptide Tools Hub

Calculators and visualizers, including a half-life and accumulation plotter for weekly-dosed peptides like pemvidutide.

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References

1. [1]

   Noureddin M, Harrison SA, Suschak JJ, et al.. “Safety and efficacy of weekly pemvidutide versus placebo for metabolic dysfunction-associated steatohepatitis (IMPACT): 24-week results from a multicentre, randomised, double-blind, phase 2b study.” Lancet. 2026. 407(10529):704-715 DOIRCT

   Peer-reviewed 24-week Phase 2b IMPACT results. n=212, biopsy-confirmed F2/F3 MASH. Met primary endpoint of MASH resolution without worsening of fibrosis; did not meet co-primary fibrosis-improvement endpoint at 24 weeks.

2. [2]

   Altimmune, Inc.. “Pemvidutide Demonstrates Significant Metabolic Improvements in Patients with MASH in New 48-Week IMPACT Phase 2b Data Presented at EASL 2026.” 2026. LinkRCT

   Company news release (not peer-reviewed) for 48-week IMPACT data at EASL 2026. Combined ELF+LSM response 27.8% (1.2 mg) / 32.4% (1.8 mg) vs. 3.2% placebo. 1.8 mg: TG −23.7%, total cholesterol −15.4%, weight loss 7.5%, BMI −3.0 kg/m², waist −5.3 cm, SBP −4.0 / DBP −2.2 mmHg.

3. [3]

   Altimmune, Inc.. “New IMPACT Phase 2b Data Highlight Concurrent Improvements Across Multiple Non-Invasive Markers and qFibrosis-Measured Fibrosis Regression with Pemvidutide in MASH at EASL 2026.” 2026. LinkRCT

   Company news release. qFibrosis (digital pathology) ≥1-stage regression at the 24-week biopsy: 68.6% (1.2 mg, p<0.001) and 54.5% (1.8 mg, p=0.002) vs. 29.6% placebo. qFibrosis figures are from 24 weeks, distinct from the 48-week non-invasive readout.

4. [4]

   Altimmune, Inc.. “Altimmune Receives FDA Breakthrough Therapy Designation for Pemvidutide in MASH.” 2026. LinkReview

   Company news release dated January 5, 2026 announcing FDA Breakthrough Therapy Designation for MASH, based on 24-week IMPACT data. A development/review status, not an approval.

5. [5]

   Harrison SA, Browne SK, Suschak JJ, et al.. “Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study.” J Hepatol. 2025. 82(1):7-17 DOI PubMedRCT

   Peer-reviewed Phase 1b 12-week MASLD study. n=94. Liver fat reduced up to 68.5% at 1.8 mg vs. 4.4% placebo; 55.6% of 1.8 mg group reached normal liver fat.

6. [6]

   Altimmune, Inc.. “Altimmune Announces Positive Topline Results from MOMENTUM 48-Week Phase 2 Obesity Trial of Pemvidutide.” 2023. LinkRCT

   Company topline release for Phase 2 MOMENTUM obesity trial. n=391. Weight loss up to 15.6% at 2.4 mg over 48 weeks vs. 2.2% placebo; only 21.9% of weight lost was lean mass. Presented at ADA 84th Scientific Sessions (262-OR).

7. [7]

   Nestor JJ, Parkes D, Feigh M, Suschak JJ, Harris MS. “Effects of ALT-801, a GLP-1 and glucagon receptor dual agonist, in a translational mouse model of non-alcoholic steatohepatitis.” Sci Rep. 2022. 12(1):6666 DOI PubMedAnimal study

   Preclinical DIO-NASH proof of concept. ALT-801 (pemvidutide) compared head-to-head with semaglutide and elafibranor; superior reductions in steatosis, inflammation, and fibrosis attributed to the glucagon arm.

8. [8]

   Nestor JJ, Zhang X, Jaw-Tsai S, et al.. “Design and characterization of a surfactant-conjugated, long-acting, balanced GLP-1/glucagon receptor dual agonist.” Pept Sci. 2021. 113(4):e24221 DOIIn vitro

   Describes pemvidutide's molecular design: a balanced (1:1) GLP-1/glucagon dual agonist with the proprietary EuPort domain for albumin binding and weekly dosing. Full amino acid sequence not publicly disclosed.

9. [9]

   World Anti-Doping Agency. “The 2026 Prohibited List — International Standard.” 2026. Link
10. [10]

    U.S. Food and Drug Administration. “FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss.” 2026. LinkSafety study

    FDA safety communication on unapproved GLP-1 products. Investigational dual agonists like pemvidutide are not approved, not prescribable, and not eligible for compounding.

11. [11]

    Altimmune, Inc.. “Altimmune Initiates PERFORMA Phase 3 Trial of Pemvidutide in Patients with MASH.” 2026. LinkReview

    Company release (August 3, 2026) announcing initiation of the registrational Phase 3 MASH trial. Two cohorts: roughly 990 biopsy-assessed participants supporting accelerated approval and roughly 800 assessed by non-invasive tests, about 1,790 total. Doses 1.2/1.8/2.4 mg. 52-week primary readout expected 2029; a roughly 60-month liver-related-events endpoint supports full approval. PERFORMA had no ClinicalTrials.gov record at the time of writing, so no NCT number is given here.

12. [12]

    Altimmune, Inc.. “Altimmune Announces Positive Topline Results from RECLAIM Phase 2 Trial of Pemvidutide in Alcohol Use Disorder.” 2026. LinkRCT

    Company topline release (July 28, 2026) for RECLAIM (NCT06987513), a 100-participant, 24-week Phase 2 trial of pemvidutide 2.4 mg vs. placebo in moderate-to-severe alcohol use disorder. Primary endpoint met (−1.45 heavy drinking days per week, p=0.0014). Drug-related discontinuations 10% vs. 0%. Not peer-reviewed; publication and conference presentation planned.

13. [13]

    Altimmune, Inc.. “Altimmune Announces Second Quarter 2026 Financial Results and Business Update.” 2026. LinkReview

    Company update (August 12, 2026). Independently restates the PERFORMA Phase 3 initiation and 2029 readout, reports that the RESTORE Phase 2 trial in alcohol-associated liver disease (approximately 120 participants, 48 weeks) completed enrollment in July 2026 with topline expected in the second half of 2027, and reports cash and investments of $519M at June 30, 2026. No update on a standalone obesity program.

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