Pemvidutide

Mechanism

Pemvidutide is a synthetic peptide dual agonist of the GLP-1 receptor and the glucagon receptor. GLP-1 receptor activation suppresses appetite, slows gastric emptying, and improves glucose-dependent insulin secretion. Glucagon receptor activation increases energy expenditure, promotes hepatic fatty acid oxidation, and reduces hepatic de novo lipogenesis. The dual mechanism is specifically designed to address both systemic metabolic dysfunction (obesity, insulin resistance) and liver-specific pathology (hepatic fat accumulation, MASH), making it distinct from GLP-1-only agonists that primarily address appetite and glycaemic control.

Evidence base

Phase 2b IMPACT Trial (Published 2025)

• IMPACT trial (PMID 41237796): 24-week randomised, double-blind Phase 2b study of pemvidutide vs placebo in biopsy-confirmed MASH (F1–F3 fibrosis).
• Significant MASH resolution and fibrosis improvement vs placebo
• ALT normalisation in a significant proportion of treated participants
• Substantial, dose-dependent reductions in hepatic fat fraction (MRI-PDFF)

Phase 2 MOMENTUM Trial — Obesity

• Dose-dependent weight reduction demonstrated, though at lower magnitude than triple agonists (e.g., retatrutide)

Mechanistic Rationale

• Balanced GLP-1/glucagon dual agonism targets both appetite/weight and hepatic fat oxidation
• Glucagon receptor activity may drive liver-specific benefits beyond what weight loss alone would achieve

Evidence grade: Moderate — based on published Phase 2b RCT data. Phase 3 confirmatory studies have not yet been initiated.

Protocols

Research use only — not approved for human use.

In the IMPACT Phase 2b trial (PMID 41237796):

• Route: Subcutaneous injection, once weekly
• Doses studied: 1.2 mg, 1.8 mg, 2.4 mg once weekly
• Titration: Gradual dose escalation to mitigate GI effects
• Duration: 24 weeks (primary endpoint); extension may follow
• Dose-escalation rationale: Reduce nausea, vomiting, diarrhoea (standard GLP-1 class effect)

No established off-trial protocols exist. All published dosing data comes from the clinical trial programme.

UK legal status

Pemvidutide is not licensed as a medicine by the MHRA and has no UK marketing authorisation for any indication. It is not a controlled substance under the Misuse of Drugs Act.

As an unlicensed, investigational peptide, it occupies a UK grey area: legal to possess for research purposes, but not approved for human therapeutic use. Vendors typically market research-grade material as 'for research use only — not for human consumption.'

The MHRA has not issued compound-specific guidance on pemvidutide. Given its Phase 2 development stage, it is unlikely to be widely available in the UK research peptide market.

Vendor notes

Pemvidutide is an investigational compound unlikely to be widely available in the UK research peptide market due to its Phase 2 development stage. Any vendor listing this compound should be treated with heightened scrutiny. Buyers should verify:

• Third-party COA availability and compound identity testing
• Vendor reputation and legitimacy (given the compound's novelty)
• Accurate compound identification (pemvidutide vs. other GLP-1 agonists)
• Compliance with UK 'research use only' framing

See our Vendor Vetting Guide for evaluation criteria.