Summary

Dapiglutide is a long-acting dual GLP-1 and glucagon receptor agonist developed by Zealand Pharma for the treatment of obesity and metabolic dysfunction-associated steatohepatitis (MASH). By co-activating GLP-1 receptors (mediating appetite suppression and glycaemic control) and glucagon receptors (mediating hepatic lipid oxidation and thermogenesis), dapiglutide aims to deliver weight loss and liver benefit beyond what GLP-1 monoagonists achieve. Phase 2 trial results have been reported, and the compound continues in clinical development. It is not a licensed medicine and has no UK marketing authorisation.

Mechanism

Dapiglutide is a long-acting dual agonist of the GLP-1 and glucagon receptors. GLP-1 receptor activation drives glucose-dependent insulin secretion, appetite suppression, and delayed gastric emptying. Glucagon receptor activation promotes hepatic fatty acid oxidation, thermogenesis, and direct reduction of hepatic steatosis. The dual mechanism is designed to achieve weight loss and hepatic benefit exceeding GLP-1 monoagonists, with GLP-1 activity offsetting glucagon's hyperglycaemic potential.

Evidence base

Evidence Grade: Moderate

Dapiglutide has completed Phase 2 clinical trials in obesity and MASH, with dose-dependent weight loss and acceptable safety reported. However, no Phase 3 data, marketing authorisation, or long-term outcome studies have been published. The evidence base is substantially smaller than for approved GLP-1 agonists such as semaglutide or tirzepatide. All findings should be considered preliminary pending late-stage confirmation.

Key evidence gaps:

  • No pivotal Phase 3 trial results
  • No cardiovascular or renal outcome data
  • No published head-to-head comparisons with approved dual/triple agonists
  • Limited independent peer-reviewed publications

Protocols

Investigational — No Approved Protocol

Dapiglutide is an unlicensed investigational compound. Clinical trial parameters (for reference only):

  • Route: Subcutaneous injection
  • Frequency: Once weekly
  • Dose: Escalating dose ranges explored in Phase 2
  • Titration: Gradual escalation to manage GI tolerability

No dosing protocol should be construed as safe or effective outside supervised clinical trials.

UK Status: Grey Area (Unlicensed Investigational Product)

Dapiglutide has no MHRA marketing authorisation. It is not a controlled substance. Sale for human consumption without a licence would breach MHRA regulations. Research-grade supply is permitted only with explicit 'research use only' labelling. See our UK Legality Guide for full context.

Vendor notes

Dapiglutide is not commercially available. No verified UK vendors sell dapiglutide as a research-grade peptide at the time of writing. Any supplier claiming to offer dapiglutide should be treated with extreme caution, as the compound is in early clinical development and bulk research-grade synthesis is not widely available. Researchers should verify any supplier claims independently.

References

  1. Zealand Pharma. Pipeline — Dapiglutide (ZE-3245). Corporate pipeline communications. Available at: https://www.zealandpharma.com/pipeline
  2. ClinicalTrials.gov. Search results for dapiglutide. Available at: https://clinicaltrials.gov/search?term=dapiglutide
  3. Gonçalves ACC, et al. Dual agonism of GLP-1 and glucagon receptors: a review of preclinical and clinical data. Curr Opin Endocrinol Diabetes Obes. 2024.
  4. Patel S, et al. Emerging peptide therapies for MASH/NASH: mechanisms and clinical progress. J Hepatol. 2024.