Pemvidutide: experimental weight-loss & fatty-liver drug (formerly ALT-801)
An injectable drug studied for obesity and fatty liver disease that targets two hunger-and-metabolism hormones at once to reduce appetite and burn liver fat; experimental, not yet an approved drug.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
Pemvidutide (formerly ALT-801; developed by Altimmune) is an investigational once-weekly injectable peptide drug being studied for fatty liver disease (MASH/MASLD), obesity, and alcohol-associated conditions. It activates two metabolic hormone receptors simultaneously — the GLP-1 receptor (the same target as semaglutide) and the glucagon receptor — in a balanced 1:1 potency ratio (Gasbjerg and colleagues, Physiological Reviews, 2026). The GLP-1 component drives appetite suppression and improved glucose control, while simultaneous glucagon-receptor engagement adds direct hepatic fat oxidation and increased energy expenditure — effects that GLP-1-selective drugs do not produce. The stored sequence here uses placeholder "X" residues for two non-standard amino acids, and the active drug additionally carries a C18 fatty-diacid lipid moiety attached through a glycosidic linker — that lipid enables albumin binding and is not represented in the raw 31-letter string.
History
Pemvidutide emerged from Altimmune's metabolic peptide program as its lead GLP-1/glucagon co-agonist candidate, initially designated ALT-801. The biological rationale traces back to oxyntomodulin, an endogenous proglucagon-derived peptide that naturally activates both GLP-1 and glucagon receptors and has been studied for decades as a model for amplifying the metabolic benefits of incretin therapy beyond GLP-1 monotherapy (Gasbjerg and colleagues, Physiological Reviews, 2026). The compound moved through Phase 1 in overweight/obese adults and into the MOMENTUM Phase 2 obesity trial and the IMPACT Phase 2b MASH trial, with key 24-week and 48-week readouts reported in 2024 (Madsbad and colleagues, Expert Opinion on Investigational Drugs, 2025; Browne and colleagues, JHEP Reports, 2025). The FDA granted pemvidutide Fast Track designation for both MASH and alcohol use disorder, and in January 2026 granted Breakthrough Therapy designation for MASH on the strength of the 24-week IMPACT data.
What it does
In treated patients, pemvidutide reduces body weight, reduces fat stored in the liver, and improves blood markers of liver injury (ALT, AST) and cardiometabolic risk (Browne and colleagues, JHEP Reports, 2025). The two halves of the molecule contribute different things. The GLP-1 component slows gastric emptying, suppresses appetite, and stimulates glucose-dependent insulin secretion. The glucagon component acts directly on the liver to increase fatty-acid oxidation and reduce fat accumulation, and increases whole-body energy expenditure (Gasbjerg and colleagues, Physiological Reviews, 2026). The balanced 1:1 receptor-potency design is the key differentiator from other peptides in the GLP-1 drug class: semaglutide (/card/pep-00016) is GLP-1-selective, tirzepatide (/card/pep-00015) is a GLP-1/GIP dual agonist, and pemvidutide sits in a third group of GLP-1/glucagon dual agonists alongside cotadutide, survodutide, and mazdutide (Madsbad and colleagues, Expert Opinion on Investigational Drugs, 2025).
Evidence
- Human (MASLD): In a 24-week randomized, double-blind, placebo-controlled trial in 64 adults with metabolic dysfunction-associated steatotic liver disease, once-weekly subcutaneous pemvidutide at 1.2 mg, 1.8 mg, and 2.4 mg produced relative liver-fat reductions on MRI-PDFF of 56.3%, 75.2%, and 76.4% respectively, versus 14.0% on placebo. Body-weight reductions were 5.1–6.2% across the pemvidutide arms versus 1.4% on placebo. Liver fat normalization (≤5%) was achieved in 30.8%, 53.8%, and 45.5% of participants at the three doses versus 0% on placebo (Browne and colleagues, JHEP Reports, 2025).
- Human (obesity): The MOMENTUM Phase 2 obesity trial randomized adults with overweight/obesity to pemvidutide 1.2, 1.8, or 2.4 mg once weekly or placebo. The 48-week mean weight reductions reported at the 84th ADA Scientific Sessions were 10.3%, 11.2%, and 15.6% at the three doses respectively, versus 2.2% on placebo, with weight loss continuing on a near-linear trajectory at end of treatment on the 2.4 mg arm (data summarized in Madsbad and colleagues, Expert Opinion on Investigational Drugs, 2025).
- Human (MASH): Topline 24-week results from the IMPACT Phase 2b trial in 212 adults with biopsy-confirmed MASH and F2/F3 fibrosis reported MASH resolution without worsening of fibrosis in 59.1% of participants on pemvidutide 1.2 mg and 52.1% on pemvidutide 1.8 mg, versus 19.1% on placebo (Altimmune topline announcement, 2024; full publication pending). These data formed the basis of the FDA Breakthrough Therapy designation.
- Mechanism context: A comparative review of the proglucagon-derived peptide family (GLP-1, glucagon, GLP-2, oxyntomodulin) and the rationale for unimolecular GLP-1/glucagon co-agonists, including pemvidutide's structural and pharmacological profile, is provided in Gasbjerg and colleagues, Physiological Reviews, 2026.
Known effects
- Liver fat reduction in MASLD — relative reductions up to ~76% at 24 weeks (Browne and colleagues, 2025)
- MASH resolution without fibrosis worsening — reported in Phase 2b topline at 24 weeks (IMPACT, 2024)
- Body-weight reduction — up to ~15.6% at 48 weeks at the 2.4 mg obesity dose (MOMENTUM, 2024; Madsbad 2025)
- Reductions in ALT and AST and improvements in non-invasive markers of liver fibrosis (Browne and colleagues, 2025)
- Improvements in serum lipid profile and blood pressure in the Phase 2 obesity program (MOMENTUM, 2024)
- No dose-titration requirement reported in Phase 2 obesity work (Madsbad and colleagues, 2025)
Safety signals
Adverse events in published Phase 2 work have been dominated by gastrointestinal effects typical of the GLP-1 drug class. In the 24-week MASLD trial, nausea occurred in 33.3% of pemvidutide-treated participants — most events mild to moderate — with treatment-discontinuation rates of 0–12.5% depending on dose; three severe adverse events were judged unrelated to the study drug (Browne and colleagues, JHEP Reports, 2025). No clinical hypoglycemia signal has been reported, consistent with the glucose-dependent nature of GLP-1-mediated insulin release. The Phase 2 obesity program reported improvements in serum lipids and blood pressure without imbalances in cardiac events or clinically meaningful increases in heart rate (MOMENTUM 2024 ADA presentation; summarized in Madsbad and colleagues, 2025). The theoretical concern from glucagon-receptor co-activation — increased hepatic glucose output — has not produced a clinical hyperglycemia signal in Phase 2.
Regulatory status
- US: Investigational. Not approved. FDA granted Fast Track designation for MASH and for alcohol use disorder; Breakthrough Therapy designation for MASH granted January 2026 based on 24-week IMPACT Phase 2b data.
- EU: Investigational. No EMA approval.
- Development phase: Phase 2 / Phase 2b across MASH (IMPACT), obesity (MOMENTUM), alcohol-associated liver disease (RESTORE), and alcohol use disorder (RECLAIM) (Madsbad and colleagues, 2025).
- WADA: Falls within the S2 prohibited class (peptide hormones and growth factors) by category; not individually listed.
Mechanism
Pemvidutide is a unimolecular 29-residue peptide with equal potency at the GLP-1 receptor and the glucagon receptor, both Gs-coupled receptors that signal through cAMP. GLP-1R engagement on pancreatic β-cells produces glucose-dependent insulin secretion, and engagement on CNS appetite circuits produces satiety. GCGR engagement on hepatocytes activates fatty-acid β-oxidation and reduces de novo lipogenesis, effects that converge on resolution of hepatic steatosis (Gasbjerg and colleagues, Physiological Reviews, 2026). The balanced 1:1 design is intended to let the GLP-1 component restrain glucagon-driven hepatic glucose output at euglycemia, preserving glycemic control, while the glucagon component delivers liver-directed and energy-expenditure effects that GLP-1 monotherapy cannot. The peptide carries a C18 fatty-diacid lipid attached through a glycosidic linker, enabling albumin binding and supporting a pharmacokinetic profile compatible with once-weekly subcutaneous dosing — a different chemical strategy from the simple γ-Glu fatty-acid spacers used by liraglutide and semaglutide (Gasbjerg and colleagues, 2026).
Open questions
- Whether the balanced 1:1 GLP-1:GCGR potency ratio produces better liver, body-composition, or weight outcomes than unbalanced GLP-1/glucagon dual agonists; head-to-head data are not available.
- Whether the MASH resolution and non-invasive fibrosis-marker improvements seen at 24 weeks translate to biopsy-confirmed fibrosis regression and durable benefit in a Phase 3 program.
- Whether glucagon-receptor co-agonism affects long-term glycemic control in patients with advanced β-cell dysfunction.
- Whether GCGR activity preserves lean mass during weight loss relative to GLP-1-selective agents — proposed but not yet established in published Phase 2 data.
Related peptides
- Semaglutide (/card/pep-00016) — GLP-1-selective agonist; the comparator framing pemvidutide's dual-agonism rationale.
- Tirzepatide (/card/pep-00015) — GLP-1/GIP dual agonist; a different "dual" architecture than pemvidutide's GLP-1/glucagon.
- Oxyntomodulin — endogenous proglucagon-derived GLP-1/glucagon co-agonist; the biological precedent for this drug class.
- Cotadutide (MEDI0382) — GLP-1/GCGR dual agonist with an unequal GLP-1-skewed potency ratio; AstraZeneca; Phase 2.
- Survodutide (BI 456906) — GLP-1/GCGR dual agonist; Boehringer Ingelheim/Zealand Pharma.
- Mazdutide (IBI362) — GLP-1/GCGR dual agonist in advanced clinical development.
- Retatrutide — GLP-1/GIP/glucagon triple agonist; broader pathway agonism, also under MASH/obesity development.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Does activating two liver receptors simultaneously with pemvidutide trigger a fat-burning program that is stronger than the sum of activating each receptor separately?
Fatty liver disease affects hundreds of millions of people and has few approved treatments. If dual activation is genuinely synergistic in the liver, pemvidutide would achieve better liver fat clearance than existing GLP-1 drugs at the same or lower doses, benefiting people with early or advanced fatty liver disease.
Could pemvidutide's dual action on liver inflammation and fat clearance interrupt the chain of events that turns fatty liver disease into liver cancer?
Fatty liver disease is now one of the most common causes of liver cancer, and there is no approved way to prevent that progression. A drug already being tested for fatty liver that could also block the path to cancer would be a major advance for the tens of millions of people at risk.
Could pemvidutide cut alcohol cravings by both dampening the brain's reward response to alcohol and correcting the low blood sugar that drives some people to drink more?
Most people with alcohol use disorder relapse partly for biological reasons that current drugs do not address. A medicine that handles both the brain's craving signal and a physical blood sugar driver could help a much larger fraction of patients stay sober.
If the glucagon-receptor activity in pemvidutide were reduced by modifying one amino acid at the front of the drug, could patients tolerate higher doses without heart rate or blood pressure increases?
Higher doses often mean better weight loss and liver fat reduction, but current dual-action drugs raise heart rate at high doses. A tuned version that keeps liver benefits without stressing the heart could help patients reach the doses where the drug works best, safely.
Do the two non-standard amino acids in pemvidutide resist enzyme breakdown on their own, separate from the fatty-acid chain that helps it last a week?
If the backbone itself resists breakdown, drug designers could use that stability scaffold with different lipid attachments or receptor profiles, potentially creating a whole family of long-acting dual metabolic drugs from the same underlying chemistry.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8760622143745422 | openfold3-mlx |
| ranking score | 0.9351562261581421 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.630 | global PDE — lower = better |
| disorder | 0.156 | fraction disordered |
| chain pair ipTM (A, B) | 0.876 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | — |
| hardware | — |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | — |
| diffusion samples | 1 |
| runtime | 541s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-30 |
▸citationbibtex
@peptide{pep10971,
sequence = {HXEGTFTSDYSKYLDSRXAAKEFIAWLVKGR},
target = {gcgr},
author = {peptidemodel},
year = {2026},
status = {computed}
}