MariTide Phase 2 results at ADA 2025

Amgen presented results from its Phase 2 obesity study of MariTide (maridebart cafraglutide) at the American Diabetes Association (ADA) 85th Scientific Sessions in June 2025. The data showed sustained weight loss of up to approximately 20% at 52 weeks, supporting the compound's advancement to Phase 3 trials.

MariTide is a first-in-class peptide-based molecule with a unique dual mechanism: it acts as a GIP receptor antagonist and a GLP-1 receptor agonist. This distinguishes it from tirzepatide, which agonises both receptors. The rationale is that blocking GIP signalling — rather than stimulating it — may produce distinct metabolic effects, particularly on fat oxidation and energy expenditure.

Key findings

The Phase 2 trial evaluated multiple dose levels of MariTide administered subcutaneously at monthly or less frequent intervals in adults with obesity. Key observations included:

  • Weight loss: Sustained reductions in body weight, with the highest dose achieving approximately 20% mean weight loss at 52 weeks
  • Dosing durability: Weight loss continued beyond the 12-week mark seen in many GLP-1 trials, suggesting an extended pharmacodynamic effect consistent with MariTide's long half-life
  • Dosing frequency: The monthly (or potentially less frequent) dosing schedule could offer a convenience advantage over the weekly injections required for semaglutide and tirzepatide

Safety signals

Adverse events were primarily gastrointestinal — nausea, vomiting, and constipation — consistent with GLP-1 receptor agonism. Amgen noted that the safety profile was manageable and broadly consistent with the GLP-1 drug class. The company reported it was refining the dosing regimen for Phase 3 to optimise tolerability.

What the unique mechanism means

MariTide's GIP receptor antagonism sets it apart from the current dual/triple agonist landscape. While tirzepatide activates both GLP-1 and GIP receptors, and retatrutide adds glucagon receptor agonism, MariTide blocks GIP while activating GLP-1. Preclinical data suggest GIP receptor blockade may enhance GLP-1-mediated weight loss and improve insulin sensitivity through complementary pathways.

The Phase 2 data provide the first robust clinical evidence that this antagonist-agonist approach can produce weight loss in the range achieved by leading dual-agonist therapies. Whether the mechanism translates to differentiated outcomes in head-to-head Phase 3 comparisons remains to be seen.

UK context

MariTide is not licensed in the UK and remains an investigational compound under Amgen's clinical development programme. Amgen is initiating Phase 3 trials that, if successful, would support regulatory submissions to the FDA, EMA, and MHRA. The monthly dosing profile, if confirmed, could be particularly relevant for NHS treatment pathways where injection frequency is a recognised barrier to adherence.

For a full compound profile, mechanism of action, and UK legal status, see our MariTide profile.

This article is for research and educational purposes only. MariTide is an investigational compound, not a licensed medicine. Nothing here constitutes medical advice.

This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.