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Pemvidutide

Altimmune's balanced 1:1 GLP-1 and glucagon dual agonist, positioned specifically for lean-mass-sparing weight loss and MASH rather than maximum scale-weight reduction.

Also known as balanced GLP-1/glucagon dual agonist, ALT-801

Human RCT — Randomised controlled trials in humans, but not an approved product for this use.

Phase 2 across obesity (MOMENTUM, about 15.6% at 48 weeks) and MASH (IMPACT, 48-week data presented at EASL 2026), plus FDA breakthrough therapy designation for MASH in January 2026. Phase 3 is planned but not complete, and the lean-mass claims come from the sponsor's own DEXA analyses rather than an independent head-to-head.

How it works

Pemvidutide's design point is receptor balance: roughly equal potency at GLPR and GCGR, in contrast to agents that lean heavily on GLP-1. The glucagon arm produces substantial hepatic fat clearance and an increase in energy expenditure, and Altimmune's central claim is that this shifts the composition of weight lost - reported lean-mass preservation of around 78-80% of total loss, compared with the roughly 60-75% typical of pure incretins. It also lowers LDL cholesterol and triglycerides more than GLP-1 monotherapy. In MASH, 48-week phase 2b IMPACT data showed improvements in non-invasive fibrosis and inflammation markers, and the FDA granted breakthrough therapy designation in January 2026.

Targets: GLP-1 receptor, Glucagon receptor

Dosing

ProtocolDoseFrequencyRoute
MOMENTUM phase 2 obesity dosingSame day each week.1.2 mg – 2.4 mgonce weeklysubcutaneous
  • · Phase 2 tested 1.2, 1.8 and 2.4 mg weekly with stepped escalation; the 2.4 mg arm gave about 15.6% mean weight loss at 48 weeks.

Titration

Stepped escalation over 4-12 weeks. The glucagon arm makes fast escalation poorly tolerated.

Cycling

Chronic therapy in design.

Work out your exact syringe units →

Pharmacology

Half-life
Supports once-weekly dosing.
Onset
Liver fat falls fast - large reductions were seen by 12 weeks in phase 1b; weight effects accrue over 24-48 weeks.
Routes
subcutaneous
Molecule
Lipidated GLP-1/glucagon receptor dual agonist peptide with EuPort delivery domain

Handling

Diluent
Bacteriostatic water for research-grade material
Typical mix
1 or 2 mL
Lyophilised
Refrigerate at 2-8 C.
Reconstituted
Refrigerated, use within about 28 days.
Light sensitive
Yes — keep it out of the light

Side effects

  • very commonNausea— Mostly mild to moderate and concentrated in escalation.
  • commonVomiting
  • commonIncreased heart rate— Glucagon-driven.
  • uncommonRise in fasting glucose in non-diabetic subjects— Glucagon-receptor effect seen in some phase 2 data.

Do not use if

  • Pregnancy.
  • History of pancreatitis - class caution.
  • Uncontrolled tachyarrhythmia.
  • Long-term human safety is not established.

Combining it

  • redundantsemaglutide — GLP-1 agonism already present.
  • redundantretatrutide — Overlapping GLP-1 and glucagon activity.
  • cautioninsulin-analogues — Mixed glycaemic effects; monitor.

What to monitor

  • · Body composition - lean-mass preservation is the entire selling point, so measure it.
  • · Liver enzymes and liver fat.
  • · Lipid panel.
  • · Heart rate.

Legal status

Investigational; not approved anywhere.

References

  • Altimmune 2024-2026, MOMENTUM phase 2 obesity trial results (trial)
  • Altimmune 2026, IMPACT phase 2b 48-week MASH data presented at EASL (trial)

Mechanism in depth

Pemvidutide's distinguishing design choice is the ratio. Most GLP-1/glucagon dual agonists are GLP-1-dominant, with the glucagon arm added as a metabolic accelerant; pemvidutide is deliberately balanced roughly 1:1, which shifts the mechanism of weight loss away from appetite suppression alone and toward energy expenditure. The sponsor's argument is that weight lost through increased energy expenditure carries a different body-composition signature than weight lost through caloric restriction, and their DEXA analyses report a substantially lower proportion of lean mass lost than incretin trials typically show - somewhere around 20-25% of total loss rather than 30-40%. That is an important claim if true, and it is worth being precise about its evidential status: it comes from the sponsor's own body-composition sub-analyses within their own trials, not from an independent head-to-head against tirzepatide or semaglutide with body composition as a pre-specified primary endpoint. The liver data is the other half of the story. The IMPACT phase 2b trial in MASH reported 24-week results in the Lancet, and pemvidutide received FDA breakthrough therapy designation for MASH in January 2026. Phase 2 weight loss in MOMENTUM was around 15.6% at 48 weeks, which is competitive but below tirzepatide. The overall positioning is a drug that is not trying to win on scale weight.

What usually goes wrong

The lean-mass claim is the thing most likely to be over-read. It comes from the sponsor's own DEXA sub-analyses, and DEXA lean-mass measurement during rapid weight loss is confounded by glycogen and water shifts. The other issues are standard for a balanced glucagon agonist: heart rate rises, fasting glucose can drift up early, and escalating too fast produces both. There is no approved product, so consumer-facing supply is unregulated.

Bloodwork worth running

MarkerWhenWhy it matters
Body composition by DEXABaseline and every 3 months.The entire pitch for this molecule is lean-mass preservation. If you are choosing it for that reason, measure it.Act if: No established threshold; the comparison that matters is the proportion of loss that is lean tissue versus what you would expect on an incretin.
ALT, AST and liver fat by MRI-PDFFBaseline, 12 weeks, 24 weeks.Liver fat falls fast and large - this was visible by 12 weeks in phase 1b.Act if: None; this is the efficacy marker for the MASH indication.
Resting heart rateDaily during escalation.A more heavily weighted glucagon arm means a more prominent chronotropic effect.Act if: More than 15 bpm above baseline means stop escalating.
Fasting glucoseBaseline and every 2-4 weeks through escalation.Balanced glucagon agonism raises hepatic glucose output more than a GLP-1-dominant agent does.Act if: A sustained rise means hold the dose.
Lipid panelBaseline and 6 months.Pemvidutide has reported unusually large LDL and triglyceride reductions in its trials, which is not typical for the class.Act if: None.

Pharmacokinetics

Crosses blood-brain barrier
partial
Accumulates
Yes — doses stack before steady state
Metabolism
Presumed proteolytic degradation; the molecule carries a lipid modification described by the sponsor as the EuPort domain, intended to improve absorption and albumin binding.
Elimination
Presumed catabolic.

Receptor targets

  • GLP-1 receptor (GLP1R) — Not verified; described as approximately 1:1 balanced with GCGR

    Appetite suppression, delayed gastric emptying, glucose-dependent insulin secretion.

  • Glucagon receptor (GCGR) — Not verified; deliberately weighted higher than in most dual agonists

    Increased resting energy expenditure, hepatic lipolysis and fatty-acid oxidation, large reductions in liver fat, and the claimed lean-mass-sparing effect. Also raises heart rate and can raise fasting glucose early.

Trials

  • IMPACT Phase 2b · 24 weeks · 2025

    Efficacy and safety of weekly pemvidutide versus placebo for metabolic dysfunction-associated steatohepatitis at 24 weeks.

  • Pemvidutide MASLD phase 1b/2a Phase 1b/2a · 24 weeks · 2025

    Large reductions in liver fat content in subjects with metabolic dysfunction-associated steatotic liver disease.

  • MOMENTUM Phase 2 · n=391 · 48 weeks · 2024

    Reported as approximately 15.6% mean weight loss at 48 weeks with a lower proportion of lean-mass loss than incretin comparators. Sponsor-reported; not confirmed against a peer-reviewed publication in this session.

What to expect, and when

Liver fat falls very fast - large reductions were visible by 12 weeks in phase 1b, which is earlier than weight loss can explain. Weight effects accrue over 24-48 weeks. Heart rate rises within the first weeks of escalation.

Stacking and comparisons

Contains a full GLP-1 arm, so redundant with semaglutide, tirzepatide, retatrutide and every other incretin. Nothing in the peptide world stacks sensibly with it. If lean-mass preservation is the reason you are interested, the interventions with far stronger evidence than any drug combination are resistance training and 1.6-2.2 g/kg protein - and the honest framing is that pemvidutide's lean-mass claim is an argument for choosing it over another drug, not a substitute for doing the work.

Against survodutide: the same two receptors with a more balanced ratio; survodutide has biopsy-confirmed fibrosis improvement and completed phase 3 obesity data, pemvidutide has breakthrough designation and a lean-mass positioning. Against tirzepatide: pemvidutide loses on weight (15.6% versus 20.9%) and claims a better body-composition profile, which is exactly the trade a well-informed person might reasonably want. Against retatrutide: retatrutide adds GIP and produces more weight loss with worse tolerability.

Rough cost

Investigational; no legitimate supply and no price.

Genuinely uncertain

  • No verifiable pharmacokinetic parameters.
  • The MOMENTUM 15.6% figure and the lean-mass proportions are sponsor communications not confirmed against a peer-reviewed publication in this session.
  • The lean-mass advantage has not been tested against an incretin in a head-to-head trial with body composition as a pre-specified primary endpoint.
  • No published titration ladder could be verified.
  • Receptor affinities and the exact GLP1R-to-GCGR ratio are not published in verifiable form.

Papers