Metabolic/Weight

Pemvidutide

Research Reagent · Laboratory Use Only

Quick Answer

What do Phase 2 clinical trials show about pemvidutide's efficacy in MASH and obesity?

Pemvidutide is a balanced 1:1 GLP-1/glucagon dual receptor agonist studied for MASH and obesity. In the Phase 2b IMPACT trial published in The Lancet (2025), pemvidutide achieved MASH resolution without fibrosis worsening in 52–58% of participants versus 20% with placebo. In the Phase 2b MOMENTUM obesity trial, pemvidutide 2.4 mg produced 15.6% weight loss at 48 weeks without dose titration. The FDA granted Breakthrough Therapy Designation for pemvidutide in MASH in January 2026.

PMID41237796↗DOI10.1016/S0140-6736(25)02114-2↗⟳ Reconstitution Calculator
Scientific AbstractPMID 41237796 · 2026

Background

Pemvidutide (ALT-801) is an investigational, unimolecular GLP-1/glucagon dual receptor agonist (1:1 balanced potency) developed by Altimmune for the treatment of obesity and metabolic dysfunction-associated steatohepatitis (MASH). IMPACT was a multicentre, randomised, double-blind, placebo-controlled Phase 2b trial enrolling 212 adults with biopsy-confirmed MASH and fibrosis stages F2/F3. Participants received subcutaneous pemvidutide 1.2 mg or 1.8 mg or placebo once weekly for 24 weeks.

Results

MASH resolution without fibrosis worsening was achieved in 58% (1.2 mg) and 52% (1.8 mg) of pemvidutide recipients versus 20% placebo (p<0.0001). Fibrosis ≥1-stage improvement without MASH worsening was achieved in 34.5% (1.8 mg) vs placebo. Significant reductions in liver fat content, ALT, and fibrosis biomarkers (ELF, PRO-C3) were observed. The FDA granted Breakthrough Therapy Designation for pemvidutide in MASH in January 2026. A registrational Phase 3 trial is planned for 2026 initiation. In parallel, the Phase 2b MOMENTUM trial (NCT05295875) demonstrated 15.6% weight loss at 48 weeks with the 2.4 mg dose in adults with obesity. Unlike semaglutide or tirzepatide, pemvidutide's balanced glucagon receptor activation drives direct hepatic fat oxidation and lipolysis, complementing GLP-1R-mediated appetite suppression.

Source:10.1016/S0140-6736(25)02114-2
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Pemvidutide?

Pemvidutide (formerly ALT-801) is an investigational unimolecular GLP-1/glucagon dual receptor agonist developed by Altimmune. It is the first balanced (1:1 potency) GLP-1R/GCGR co-agonist to demonstrate significant efficacy in both Phase 2b obesity (MOMENTUM) and MASH (IMPACT) trials. The FDA granted Breakthrough Therapy Designation for pemvidutide in MASH in January 2026.

Mechanism of Action

Pemvidutide is a 29-amino acid peptide modified with Altimmune's proprietary EuPort™ glycolipid moiety, which extends half-life to enable once-weekly subcutaneous dosing without requiring dose titration. Its dual mechanism activates two complementary metabolic pathways:

  • GLP-1 receptor (GLP-1R) agonism: Suppresses appetite via hypothalamic satiety pathways, slows gastric emptying, enhances glucose-dependent insulin secretion, and reduces post-meal glucagon.
  • Glucagon receptor (GCGR) agonism: Drives direct hepatic lipid oxidation and ketogenesis, increases energy expenditure through thermogenesis, promotes lipolysis from adipose tissue, and reduces liver fat content independent of caloric restriction.

The balanced 1:1 receptor potency — distinguishing pemvidutide from primarily GLP-1-dominant agents — is designed to maximise the hepatoprotective component of glucagon receptor signalling, making it particularly relevant for MASH pathology.

Observed Clinical Results

  • MASH (IMPACT Phase 2b): MASH resolution without fibrosis worsening in 58% (1.2 mg) and 52% (1.8 mg) vs 20% placebo; ≥1-stage fibrosis improvement in 34.5% (1.8 mg).
  • Obesity (MOMENTUM Phase 2b): Mean weight loss of 15.6% at 48 weeks (2.4 mg dose) vs 2.2% placebo; 78.6% reduction in liver fat at the high dose.
  • Lipid profile: Significant reductions in triglycerides and LDL-C; improvements in HDL-C.
  • No dose titration required: Rapid, linear weight loss from week 1, without the typical 16–20 week titration period of GLP-1 receptor agonists.

Regulatory Status

  • FDA Breakthrough Therapy Designation for MASH (January 2026)
  • End-of-Phase 2 meeting with FDA for obesity completed in 2026
  • Registrational Phase 3 programme planned across MASH and obesity indications
Clinical Research Parameters
2 trials2 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT05989711 ↗
COMPLETEDPhase IIn=212

Safety and Efficacy of Pemvidutide in Metabolic Dysfunction-Associated Steatohepatitis (MASH) — IMPACT Phase 2b

IMPACT is a multicentre, randomised, double-blind, placebo-controlled Phase 2b study evaluating once-weekly subcutaneous pemvidutide (1.2 mg or 1.8 mg) versus placebo for 24 weeks in adults with biopsy-confirmed MASH and fibrosis stages F2/F3. Primary results published in The Lancet (2025, PMID 41237796): MASH resolution without fibrosis worsening was achieved in 58% (1.2 mg) and 52% (1.8 mg) of pemvidutide-treated participants versus 20% with placebo (p<0.0001 for both). Fibrosis improvement of ≥1 stage achieved in 34.5% (1.8 mg) vs placebo. The FDA granted Breakthrough Therapy Designation for pemvidutide in MASH in January 2026. Phase 3 registrational trial in MASH planned for 2026 initiation.

Study Interventions
Pemvidutide 1.2 mg, Pemvidutide 1.8 mg, Placebo
Primary Endpoints
MASH resolution without worsening of fibrosis at week 24; ≥1-stage fibrosis improvement without worsening of MASH at week 24
Study Period
2023-07 → 2025-04
NCT05295875 ↗
COMPLETEDPhase IIn=391

A Phase 2 Study to Evaluate the Safety and Efficacy of ALT-801 (Pemvidutide) in Adults With Obesity or Overweight — MOMENTUM

MOMENTUM is a randomised, double-blind, placebo-controlled Phase 2b study evaluating once-weekly subcutaneous pemvidutide at 1.2 mg, 1.8 mg, and 2.4 mg versus placebo in adults with obesity or overweight over 48 weeks. Results presented at ADA 84th Scientific Sessions (2024): mean weight loss of 10.3%, 11.2%, and 15.6% at 1.2 mg, 1.8 mg, and 2.4 mg respectively versus 2.2% with placebo at week 48. Significant reductions in liver fat (up to 78.6% at high dose) and favourable lipid profile improvements observed. Altimmune completed end-of-Phase 2 meeting with FDA in 2026, advancing towards Phase 3 in obesity.

Study Interventions
Pemvidutide 1.2 mg, Pemvidutide 1.8 mg, Pemvidutide 2.4 mg, Placebo
Primary Endpoints
Percent change from baseline in body weight at week 48
Study Period
2022-05 → 2024-06
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Pemvidutide is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 41237796) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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