# MariTide > Amgen’s once-monthly antibody–peptide conjugate — a GIP-receptor-blocking antibody carrying two GLP-1 agonist peptides. Phase 2 reported up to ~20% weight loss at 52 weeks; Phase 3 MARITIME is running. - Also known as: Maridebart cafraglutide, AMG 133 - Class: Metabolic - FDA approved: No - Canonical page: https://americanpeptide.com/catalog/maritide ## Overview MariTide (maridebart cafraglutide) is an investigational bispecific molecule that does something no other incretin drug does: it blocks the GIP receptor while activating the GLP-1 receptor. Structurally it is a monoclonal antibody against the GIP receptor with two GLP-1 analog peptides chemically attached, and the antibody scaffold gives it a half-life long enough for monthly — possibly less frequent — dosing. The Phase 2 trial (NEJM 2025) reported up to ~20% mean weight reduction at 52 weeks without a plateau. Amgen’s Phase 3 MARITIME program is ongoing; it is not approved. MariTide sits at the center of an unresolved question in incretin biology. Tirzepatide activates the GIP receptor and produces more weight loss than GLP-1 alone; MariTide blocks the same receptor and also produces large weight loss. Human genetics motivated Amgen’s choice — variants that reduce GIP-receptor function are associated with lower body-mass index — and one proposed reconciliation is that sustained agonism desensitizes the receptor, so both approaches end up reducing GIP signaling. The question is not settled. It is an antibody–peptide conjugate: a fully human monoclonal antibody that binds and blocks the GIP receptor, with two GLP-1 analog peptides joined to it through linkers. At roughly 150 kDa it is produced in mammalian cell culture and then conjugated — manufacturing closer to an antibody–drug conjugate than to a synthetic peptide. In the Phase 2 trial (Jastreboff et al., NEJM 2025), adults with obesity and without diabetes lost up to about 20% of body weight at 52 weeks on monthly dosing, with weight still falling at the end of treatment; those with type 2 diabetes lost up to about 17%. Early dose escalation was marked by frequent nausea and vomiting, which the Phase 3 program addresses with slower titration. The Phase 3 MARITIME trials are enrolling across obesity, type 2 diabetes and related conditions, with first data expected in 2027; no regulatory filing has been made. ## Mechanism Antagonism of the GIP receptor by the antibody domain combined with GLP-1 receptor agonism by two conjugated peptide arms. The antibody’s FcRn recycling extends exposure to weeks. ## Chemistry | Property | Value | | --- | --- | | Molecular weight | 150000 Da | ## Research areas Studied in: Obesity, Type 2 diabetes, Long-interval dosing, Weight maintenance. Guides on this site: - [Weight Loss & Metabolic Health](https://americanpeptide.com/research-areas/weight-loss): Incretin and metabolic peptides studied for glycemic control and fat loss. ## Key research - GIP-receptor antagonism plus GLP-1 agonism — the opposite GIP strategy to tirzepatide, motivated by human genetic data. - Antibody–peptide conjugate — a GIPR-blocking monoclonal antibody carrying two GLP-1 analog peptides; ~150 kDa. - Phase 2 (NEJM 2025, 52 weeks) — up to ~20% mean weight reduction in obesity without diabetes and ~17% with type 2 diabetes, without a plateau. - Monthly dosing — antibody pharmacokinetics support once-monthly injection; less frequent maintenance schedules are under study. - Status — Phase 3 MARITIME program ongoing, first data expected 2027; investigational. ## Storage, handling & synthesis **Storage.** Stored refrigerated (2–8 °C), protected from light and freezing, not shaken; investigational handling per trial protocol. **Handling.** A large antibody conjugate sensitive to freezing, heat and agitation, which can cause aggregation. ## FAQs ### What is MariTide? MariTide (maridebart cafraglutide, AMG 133) is Amgen’s investigational once-monthly obesity drug — an antibody that blocks the GIP receptor, linked to two peptides that activate the GLP-1 receptor. ### Is MariTide a peptide? Partly. It is an antibody–peptide conjugate: a ~150 kDa monoclonal antibody with two GLP-1 analog peptides attached. It cannot be made by peptide synthesis alone. ### How can blocking GIP and activating GIP both cause weight loss? This is genuinely unresolved. Tirzepatide activates the GIP receptor; MariTide blocks it; both reduce weight. One hypothesis is that chronic agonism desensitizes the receptor so that both strategies lower GIP signaling over time. Human genetic data linking reduced GIP-receptor function to lower BMI motivated the antagonist approach. ### How much weight do people lose on MariTide? The Phase 2 trial (NEJM 2025) reported up to about 20% mean weight reduction at 52 weeks in adults with obesity without diabetes, and about 17% in those with type 2 diabetes. Phase 3 results are not yet available. Population means, not individual predictions. ### Is MariTide approved? No. It is investigational, in the Phase 3 MARITIME program, and no regulatory filing has been made. This page is a research reference, not medical advice. ## Latest research Recent trials and publications mentioning MariTide, pulled automatically from ClinicalTrials.gov and PubMed (unfiltered search results, refreshed daily). ### Recent trials - [Home Self-administration of Maridebart Cafraglutide With Autoinjector in Adults Living With Obesity or Overweight](https://clinicaltrials.gov/study/NCT07871409) — RECRUITING · PHASE3 · NCT07871409 - [Efficacy, Safety and Tolerability of Switching From Glucagon-like Peptide-1 Receptor Agonists (GLP-1RA) to Maridebart Cafraglutide in Adults With Obesity or Overweight (MARITIME-SWITCH)](https://clinicaltrials.gov/study/NCT07575399) — RECRUITING · PHASE3 · NCT07575399 - [Comparing the Extent to Which Maridebart Cafraglutide (AMG 133) is Made Available in the Body When Administered Using Two Subcutaneous Presentations After Multiple Doses](https://clinicaltrials.gov/study/NCT07921316) — NOT_YET_RECRUITING · PHASE1 · NCT07921316 - [Maridebart Cafraglutide Versus Semaglutide in Participants With Type 2 Diabetes](https://clinicaltrials.gov/study/NCT07866066) — RECRUITING · PHASE3 · NCT07866066 - [Comparing the Extent to Which Maridebart Cafraglutide is Made Available in the Body of Participants Living With Overweight or Obesity After Switching From Glucagon-like Peptide-1 Receptor Agonists (GLP-1RA)](https://clinicaltrials.gov/study/NCT07908316) — RECRUITING · PHASE1 · NCT07908316 - [Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity](https://clinicaltrials.gov/study/NCT07037433) — ACTIVE_NOT_RECRUITING · PHASE3 · NCT07037433 --- Source: AmericanPeptide.com — https://americanpeptide.com/catalog/maritide Data license: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Attribution: AmericanPeptide.com. Research reference only — computational and educational content, not medical advice.