{"id":"pemvidutide","name":"Pemvidutide","aliases":["ALT-801","GLP-1/glucagon dual agonist"],"url":"https://lyoresearch.com/compounds/pemvidutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Pemvidutide is a once-weekly peptide agonist at both the GLP-1 and glucagon receptors, developed by Altimmune for metabolic dysfunction-associated steatohepatitis (MASH). In IMPACT, a 212-patient phase 2b published in The Lancet in 2025, MASH resolved without worsening of fibrosis in 52–58% of treated patients against 20% on placebo at 24 weeks. The second endpoint — fibrosis improvement — was not met at either dose. It is not approved anywhere.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"1 phase 2b RCT published (IMPACT, n=212)","regulatory_status":"Investigational (phase 2b)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"sequence":null,"sequence_note":null,"note":"No PubChem record: the structure of this investigational peptide has not been deposited"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous injection, once weekly","half_life":"Consistent with weekly dosing; no figure recorded by LYO from a source it has read","licensed_regimen":null,"product":null,"source":{"title":"IMPACT phase 2b trial (Lancet, 2025)","url":"https://pubmed.ncbi.nlm.nih.gov/41237796/"}},"outcomes":[{"outcome":"MASH resolution without worsening fibrosis","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 2b RCT (n=212, 24 wk)","evidence":"IMPACT randomised 212 patients with biopsy-confirmed MASH and F2–F3 fibrosis to one of two weekly doses or placebo for 24 weeks. Resolution without fibrosis worsening reached 58% and 52% against 20% on placebo — differences of 38 and 32 percentage points, both highly significant, on paired biopsies.","references":[{"citation":"Noureddin M, et al. Pemvidutide, a GLP-1/glucagon dual receptor agonist, in patients with metabolic dysfunction-associated steatohepatitis (IMPACT): a randomised, double-blind, placebo-controlled, phase 2b trial.","where":"Lancet, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/41237796/"}],"verbatim":{"text":"MASH resolution without fibrosis worsening was observed in 18 (20%) of 86 patients in the placebo group, 24 (58%) of 41 patients in the 1·2 mg pemvidutide group (difference of 38% [95% CI 21-56]; p<0·0001), and 45 (52%) of 85 patients in the 1·8 mg pemvidutide group (difference of 32% [95% CI 19-46]; p<0·0001).","citation":"Noureddin M, et al. Pemvidutide, a GLP-1/glucagon dual receptor agonist, in patients with metabolic dysfunction-associated steatohepatitis (IMPACT): a randomised, double-blind, placebo-controlled, phase 2b trial.","url":"https://pubmed.ncbi.nlm.nih.gov/41237796/"}},{"outcome":"Fibrosis improvement","grade":"B","grade_meaning":"probable, not settled","effect_size":"not measurable","adverse":false,"human_studies":"1 phase 2b RCT (n=212, 24 wk)","evidence":"The other half of the result, and the part that matters most for liver outcomes: fibrosis improvement without worsening of MASH was no better than placebo at either dose, with confidence intervals crossing zero. Twenty-four weeks is short for fibrosis to change, which is the sponsor's explanation and remains an explanation rather than a finding.","references":[{"citation":"Noureddin M, et al. Pemvidutide, a GLP-1/glucagon dual receptor agonist, in patients with metabolic dysfunction-associated steatohepatitis (IMPACT): a randomised, double-blind, placebo-controlled, phase 2b trial.","where":"Lancet, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/41237796/"}],"verbatim":{"text":"Fibrosis improvement without worsening of MASH was observed in 24 (28%) of 86 patients in the placebo group, 13 (33%) of 41 patients in the 1·2 mg pemvidutide group (difference of 5% [95% CI -13 to 22]; p=0·59), and 30 (36%) of 85 patients in the 1·8 mg pemvidutide group (difference of 8% [95% CI -6 to 22]; p=0·27).","citation":"Noureddin M, et al. Pemvidutide, a GLP-1/glucagon dual receptor agonist, in patients with metabolic dysfunction-associated steatohepatitis (IMPACT): a randomised, double-blind, placebo-controlled, phase 2b trial.","url":"https://pubmed.ncbi.nlm.nih.gov/41237796/"}},{"outcome":"Weight loss","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"Phase 2 programme","evidence":"Weight loss accompanies the liver effect, as it does with every incretin agonist tested in MASH, and the glucagon component adds energy expenditure to appetite suppression. Pemvidutide's obesity trials are earlier-phase than its liver programme, which is why this row is C.","references":[]},{"outcome":"GI side effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":true,"human_studies":"1 phase 2b RCT (n=212)","evidence":"The class profile — nausea, vomiting, diarrhoea concentrated in dose escalation. Nothing in the phase 2b separates it from the other incretin agonists on tolerability.","references":[]}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational."},{"region":"United States","status":"Not approved","note":"Investigational, phase 2b complete. Products sold under the name are not the trial drug."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so S0 (non-approved substances)."}],"faq":[{"q":"Did pemvidutide work in MASH?","a":"On one of its two endpoints, convincingly: MASH resolved in about half of treated patients against a fifth on placebo, on paired biopsies. On fibrosis it did nothing measurable at 24 weeks. Both results come from the same published phase 2b."},{"q":"Why does the glucagon receptor matter?","a":"Glucagon acts on the liver to burn fat and raises energy expenditure. Adding it to a GLP-1 agonist is an attempt to clear liver fat faster than appetite suppression alone would — the reason this class is being developed for liver disease first."},{"q":"Is pemvidutide available?","a":"No. It is investigational everywhere, and anything sold under the name outside a trial is not the trial drug."}],"references":[{"cite":"Noureddin M, et al. Pemvidutide, a GLP-1/glucagon dual receptor agonist, in patients with metabolic dysfunction-associated steatohepatitis (IMPACT): a randomised, double-blind, placebo-controlled, phase 2b trial.","where":"Lancet, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/41237796/","note":"212 randomised, biopsy-confirmed MASH with F2–F3 fibrosis, 24 weeks. NCT05989711. Resolution endpoint met; fibrosis endpoint not met."}],"last_reviewed":"2026-10-29","literature_searched_to":"2026-10-29","changelog":[{"date":"2026-10-29","note":"Initial publication. Grade B on a published phase 2b: resolution endpoint met at both doses, fibrosis endpoint missed at both."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}