MariTide (maridebart cafraglutide)
Also known as: maridebart cafraglutide, AMG 133, GIPR antagonist / GLP-1R agonist antibody-peptide conjugate
Overview
MariTide (maridebart cafraglutide, formerly AMG 133) is a novel bispecific antibody-peptide conjugate developed by Amgen, engineered to simultaneously antagonize the GIP receptor (GIPR) and agonize the GLP-1 receptor (GLP-1R). Unlike tirzepatide (which is a GIPR agonist/GLP-1R agonist), MariTide's GIPR antagonism is a contrarian approach based on evidence that blocking GIP signaling in the obese state may reduce fat storage and synergize with GLP-1 effects. Its antibody backbone provides a long elimination half-life of 14–24 days, enabling once-monthly or potentially less frequent (quarterly) subcutaneous dosing — a major differentiator from all weekly-injection competitors. Phase 2 data (52 weeks) showed up to ~20% weight loss in people with obesity without T2D and ~17% in those with T2D, without a weight-loss plateau at 52 weeks. The MARITIME Phase 3 program, one of the largest in Amgen's history, is actively enrolling across 6 global studies.
Mechanism of Action
Bispecific antibody-peptide conjugate: (1) anti-GIPR monoclonal antibody backbone antagonizes GIP receptor to reduce fat storage and synergize with GLP-1 effects; (2) two conjugated GLP-1 agonist peptides activate GLP-1R for appetite suppression and glucose lowering. The IgG2 backbone provides ~14–24 day half-life, enabling monthly dosing. This contrasts with tirzepatide's GIPR agonism, representing a fundamentally different pharmacological approach to the GIP pathway.
Potential Benefits
- Phase 2: up to ~20% weight loss at 52 weeks (obesity without T2D, efficacy estimand)
- Phase 2: up to ~17% weight loss at 52 weeks (obesity with T2D)
- No weight-loss plateau observed at 52 weeks — trajectory continuing downward
- Once-monthly or potentially once-quarterly subcutaneous dosing (major differentiator)
- Phase 1: 14.5% weight loss in 12 weeks at highest MAD dose (420 mg q4w)
- HbA1c reductions up to 2.2% in T2D patients (Phase 2)
- Significant reductions in fat mass: 26–37% reduction in body fat (obesity without T2D)
- Durability signal: weight maintained for months after discontinuation in some patients
- Cardiometabolic improvements: waist circumference, blood pressure, hs-CRP, lipids
- Potential for quarterly dosing — Phase 2 Part 2 showed durable maintenance efficacy
Research Dosage Notes
The following reflects doses used in published research studies. This is not medical advice.
Consult published research literature for study-specific protocols.
Routes of Administration
Subcutaneous Injection High (antibody-based; SC bioavailability typical of mAb therapeutics ~70–80%)
Once-monthly (every 4 weeks) SC injection; potential for quarterly dosing demonstrated in Phase 2 Part 2. Mean half-life 14–16 days (intact conjugate); 21–24 days (total antibody). Tmax 4–7 days post-dose.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving MariTide (maridebart cafraglutide):
Metabolic Health Stack
Combines MariTide (maridebart cafraglutide) with MOTS-c (mitochondrial metabolism) and AOD-9604 (lipolysis) for metabolic optimization.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Storage | Refrigerate at 2-8°C after reconstitution. Do not freeze reconstituted solution. |
|---|
Typical vial sizes: 5 mg. Add bac water slowly down the side of the vial, swirl gently — do not shake. Use insulin syringe for precise dosing.
Need exact syringe measurements?
Amino Acid Sequence
Proprietary — two GLP-1 analog peptide moieties (cafraglutide) conjugated to a human anti-GIPR IgG2 monoclonal antibody
Side Effects & Safety
- Nausea and vomiting (most common; dose-dependent; substantially reduced with optimized dose escalation)
- Diarrhea
- Decreased appetite
- Injection site reactions
- GI adverse events are class effects of GLP-1 agonism
- Safety profile consistent with GLP-1 receptor agonist class
- No new or unexpected safety signals in Phase 1 or 2
- No clinically significant blood pressure or ECG changes
- Immunogenicity monitoring ongoing (antibody therapeutic)
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
MTC/MEN2
Contains a GLP-1 receptor agonist component. Contraindicated in patients with personal or family history of MTC or MEN2.
Severe GI Disorders
GIPR antagonism combined with GLP-1 agonism may cause significant GI effects. Use caution in patients with inflammatory bowel disease or severe gastroparesis.
Pregnancy & Lactation
Not studied in pregnancy. Due to long-acting antibody-peptide conjugate format, extended washout period required before conception.
Drug Interactions
- Insulin/sulfonylureas: Risk of hypoglycemia. Monitor blood glucose closely.
Pharmacokinetics
| Half-Life | 14–16 days (intact conjugate); 21–24 days (total antibody) — enables monthly or quarterly dosing |
|---|---|
| Storage | Refrigerate at 2–8°C; do not freeze; protect from light (standard antibody therapeutic storage) |
Synergistic Compounds
The following compounds have been studied alongside MariTide (maridebart cafraglutide) for potential complementary or synergistic effects:
Learn More
References & Further Reading
- Phase 2 MariTide results: up to ~20% weight loss without plateau at 52 weeks — ADA 2025
- A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings
- Phase I results for AMG 133 — Nature Reviews Endocrinology
- AMG 133 weight loss drug shows promise in Phase 1 trial
- Inside Amgen's Phase 3 MARITIME Program
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