MariTide (AMG 133): Monthly GLP-1R Agonist / GIPR Antagonist
Amgen’s bispecific peptide-antibody conjugate combining GLP-1 agonism with GIP receptor blockade. Monthly dosing, Phase 3 ongoing.
👥 Human studies
- Full name
- MariTide (AMG 133, maridebart cafraglutide)
- Class
- GLP-1R agonist / GIPR antagonist peptide-mAb conjugate
- Half-life
- ~21 days
- Route
- Subcutaneous monthly
- Developer
- Amgen
- Regulatory status
- Phase 3 MARITIME-1/2 fully enrolled; obesity readouts expected 2027. Phase 2 Part 2: up to ~20% weight loss maintained over 2 years. Amgen.
What it is
MariTide is an antibody-peptide conjugate in which two GLP-1 agonist peptides are linked to a monoclonal antibody that blocks the GIP receptor. It is the first clinical compound to combine GLP-1 agonism with GIP antagonism — the opposite GIP arm of tirzepatide.
How it works
GLP-1 agonism produces the familiar satiety and glucose-dependent insulin response. GIP antagonism is hypothesised to reduce obesogenic effects of GIP on adipose tissue and blunt counter-regulatory weight regain.
The antibody scaffold provides a ~3-week half-life enabling monthly dosing — a practical advantage over weekly GLP-1s for long-term adherence.
What the research shows
Phase 1 and Phase 2 results in 2024 generated strong attention; Phase 3 started late 2024.
Veñiant M. et al. (2024) — Phase 1 AMG 133
Nature Metabolism 2024;6:290–303. 👥 Human studies
49 obese adults received single doses up to 420 mg or multiple doses of 280 mg monthly for 12 weeks.
Mean weight loss 14.5% at week 12 after only three doses — remarkable for such short exposure. Nausea and vomiting were the main adverse events.
Limitations: Small Phase 1; open-label arms; very short follow-up.
Phase 2 topline (Amgen press release, November 2024)
Amgen corporate communication; full publication pending. 👥 Human studies
592 obese adults (with and without T2D). Monthly MariTide for 52 weeks produced up to 20% mean weight loss in non-diabetic participants and ~17% in T2D.
No plateau was observed at 52 weeks, suggesting the curve may still be descending — different from Phase 3 GLP-1 monotherapies where plateau begins around month 9.
Limitations: Peer-reviewed publication pending; discontinuation rates due to GI side effects 11–26%.
Safety and limitations
GI tolerability is the main concern: nausea and vomiting mirror other incretins but with a dose-escalation challenge owing to monthly fixed dosing. Future protocols include starting dose titration schemes.
Long-term effects of chronic GIP antagonism in humans are unknown — GIP has physiological roles in bone and fat metabolism.