Maridebart Cafraglutide (MariTide)
Medium EvidenceAmgen's once-monthly injectable GIP receptor antagonist and GLP-1 receptor agonist, showing up to 20% weight loss in phase 2 trials with a unique mechanism that blocks GIP while activating GLP-1.
What It Is
Maridebart cafraglutide (MariTide) is a bispecific antibody-peptide conjugate developed by Amgen that combines GIP receptor antagonism with GLP-1 receptor agonism in a single once-monthly injectable molecule. Unlike dual agonists such as tirzepatide that activate both GIP and GLP-1 receptors, MariTide takes the opposite approach to GIP — blocking it rather than stimulating it. This unique mechanism challenges the prevailing hypothesis that GIP agonism contributes to weight loss and suggests that GIP antagonism may provide complementary metabolic benefits. Phase 2 results published in the New England Journal of Medicine demonstrated mean weight reductions of up to 20% in participants with obesity at 52 weeks, with no weight-loss plateau observed, indicating potential for continued weight reduction beyond one year. In participants with type 2 diabetes and obesity, weight loss reached up to 17% with HbA1c reductions of up to 2.2 percentage points. Full Phase 2 results were presented at the American Diabetes Association 85th Scientific Sessions in 2025, confirming dose-dependent weight loss across all cohorts. The once-monthly dosing schedule represents a significant convenience advantage over weekly injectables in the GLP-1 class. Amgen launched the MARITIME Phase 3 program in 2025, comprising six global studies evaluating MariTide across obesity/overweight (MARITIME-1), type 2 diabetes with obesity (MARITIME-2), cardiovascular outcomes, heart failure, kidney disease, and obstructive sleep apnea. As of May 2026, enrollment is advancing across the MARITIME program, with Phase 3 results expected in 2027–2028. MariTide is not yet FDA-approved for any indication and remains an investigational new drug.
Regulatory Status
Currently in the MARITIME phase 3 clinical program. MARITIME-1 evaluates obesity/overweight; MARITIME-2 evaluates type 2 diabetes with obesity. Additional phase 3 studies target cardiovascular, heart failure, kidney disease, and OSA outcomes. No FDA approval yet.
Effective: 2025
View FDA SourceWhy Researchers Study It
MariTide's GIP antagonist/GLP-1 agonist mechanism is mechanistically distinct from every other incretin-based obesity therapy. Its once-monthly dosing and absence of a weight-loss plateau at 52 weeks make it a compelling candidate for long-term obesity management. Researchers are particularly interested in whether GIP antagonism provides metabolic advantages over GIP agonism, and whether the antibody-peptide conjugate format can extend pharmacodynamic activity beyond what traditional peptide modifications achieve.
Proposed Mechanisms
- Antagonizes GIP receptors, potentially reducing GIP-mediated lipogenesis and adipose tissue expansion
- Activates GLP-1 receptors to promote satiety, slow gastric emptying, and enhance insulin secretion
- Antibody-peptide conjugate format extends half-life to enable once-monthly dosing
- Dual mechanism may reduce compensatory hunger rebound observed with GLP-1-only agents
- Continued weight loss without plateau at 52 weeks suggests sustained metabolic adaptation
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Phase 2 RCT | Adults with obesity, no T2D (52 weeks) | Up to 20% mean weight loss with no plateau; dose-dependent response across multiple dose levels | Source |
| Phase 2 RCT | Adults with obesity and T2D (52 weeks) | Up to 17% mean weight loss; HbA1c reduction up to 2.2 percentage points | Source |
| Phase 3 (ongoing) | MARITIME-1: obesity/overweight, 72 weeks | Enrollment ongoing; primary endpoint is percent change in body weight | Source |
Commonly Discussed Benefits
Safety & Cautions
- Not yet FDA-approved — all data is from clinical trials
- Phase 2 gastrointestinal side effects (nausea, vomiting, diarrhea) were consistent with GLP-1 class effects
- Long-term safety beyond 52 weeks not yet established
- GIP antagonism is a novel mechanism with limited long-term human data
- Phase 3 MARITIME results expected 2027–2028
Comparisons
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Citations
- [1] Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial. NEJM 2026 PubMed
- [2] Once-Monthly Maridebart Cafraglutide in Obesity — A Phase 2 Trial (Correspondence). NEJM 2026 PubMed
- [3] Amgen MARITIME Phase 3 Program Overview PubMed
- [4] ClinicalTrials.gov — MARITIME-1 Study (NCT06858878) PubMed
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