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The opposite bet to tirzepatide — block GIP rather than activate it — delivered once a month on an antibody.
Also known as: MariTide · AMG 133 · AMG133
Part of the Metabolic & GLP-1 peptides cluster
Overview
Maridebart cafraglutide (MariTide, AMG 133) is an investigational antibody–peptide conjugate from Amgen: an antibody that antagonises the GIP receptor carrying two GLP-1 receptor agonist peptides. Dosed once monthly, it produced 12.3% to 16.2% weight loss at 52 weeks in a phase 2 trial in obesity versus 2.5% with placebo, and is in phase 3 as of September 2026.
Source & context
Biological / chemical source: Engineered conjugate: an anti-human GIPR antagonist antibody carrying two GLP-1 receptor agonist peptides (cafraglutide)
Primary research or clinical context: Investigational (Amgen) — phase 3 MARITIME programme in obesity, type 2 diabetes, cardiovascular outcomes and sleep apnoea; once-monthly dosing
What maridebart cafraglutide is
Maridebart cafraglutide (AMG 133), known as MariTide, is an anti-human GIP receptor antagonist antibody with two attached GLP-1 agonist peptides, cafraglutide. It is proposed to elicit synergistic effects — antagonism of GIPR signalling plus activation of GLP-1 receptor signalling — to regulate body weight in obesity (IUPHAR ligand 13316, classified as an antibody). It is included in this directory because its active pharmacology runs through peptides and because it sits at the centre of the class's central paradox: tirzepatide activates the GIP receptor and loses weight; MariTide blocks it and also loses weight.
The GIPR paradox
Both GIPR agonism (tirzepatide) and GIPR antagonism (maridebart cafraglutide) have paradoxically shown significant weight-loss effects in humans (Davies et al., Diabetes, Obesity and Metabolism 2026). Preclinical and phase 1 work showed that a GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters (Véniant et al., Nature Metabolism 2024), and reviews of GLP-1/GIP combination therapies treat the resolution of this paradox as an open question in incretin biology (Davies et al., Annual Review of Nutrition 2026; Son et al., Endocrine Reviews 2026).
Phase 2: once-monthly dosing
The phase 2 trial enrolled 592 participants in 11 groups. In the obesity cohort (465 participants, mean BMI 37.9), doses of 140, 280 or 420 mg every 4 weeks, 420 mg every 8 weeks, or 420 mg with 4- or 12-week dose escalation produced mean weight change at week 52 ranging from −12.3% to −16.2% versus −2.5% with placebo. In the obesity–diabetes cohort (127 participants), weight fell by −8.4% to −12.3% versus −1.7%, with HbA1c reductions of 1.2 to 1.6 percentage points versus 0.1. Gastrointestinal adverse events were common but less frequent with dose escalation and a lower starting dose; no unexpected safety signals emerged (Jastreboff et al., New England Journal of Medicine 2025).
| Cohort | Maridebart cafraglutide (range across arms) | Placebo |
|---|---|---|
| Obesity (n=465) | −12.3% to −16.2% | −2.5% |
| Obesity with type 2 diabetes (n=127) | −8.4% to −12.3% | −1.7% |
| HbA1c, obesity–diabetes cohort | −1.2 to −1.6 pts | +0.1 pts |
Phase 3: the MARITIME programme
ClinicalTrials.gov lists 25 studies as of September 2026, including phase 3 trials in obesity and overweight with and without type 2 diabetes with long-term extensions (NCT07684144, NCT07684235), a cardiovascular outcomes trial in atherosclerotic disease (NCT07037433), a trial in obstructive sleep apnoea (NCT07226765), a study of switching from GLP-1 receptor agonists (NCT07575399) and a bioavailability study of alternative presentations (NCT07313761).
MariTide vs tirzepatide vs retatrutide
Cross-trial and indicative only: MariTide reached up to −16.2% at 52 weeks in phase 2; tirzepatide reached −20.9% at 72 weeks in SURMOUNT-1; retatrutide reached −24.2% at 48 weeks in phase 2. MariTide's distinctive features are the monthly (or two-monthly) schedule, which follows from the antibody's long circulation, and the antagonist rather than agonist approach to GIP. The tirzepatide and retatrutide profiles cover the agonist side of the paradox.
Status and what this page is not
Maridebart cafraglutide is investigational and not approved anywhere as of September 2026. As an antibody conjugate it cannot be synthesised as a research peptide, and nothing sold under the MariTide name outside Amgen's trials corresponds to the molecule. This profile is educational and not medical advice.
Structure & chemistry
Molecular identity & reference confidence
Reference mass unavailable
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Monoclonal antibody scaffold with two attached GLP-1 agonist peptides; classified by IUPHAR as an antibody
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-09-07
- Plasma half-life
- Supports once-monthly (every 4 weeks) or every-8-weeks dosing in phase 2
- Receptors
- GIP receptor (antagonised by the antibody) and GLP-1 receptor (activated by the conjugated cafraglutide peptides)
- Backbone
- Monoclonal antibody scaffold with two attached GLP-1 agonist peptides; classified by IUPHAR as an antibody
- Status
- Investigational: phase 3 MARITIME programme (obesity, type 2 diabetes, cardiovascular outcomes, obstructive sleep apnoea, switching from GLP-1 agonists); not approved as of September 2026
- IUPHAR ligand: 13316
- CAS RN: 2760218-55-9
Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology · fetched 2026-09-07.
Clinical development snapshot
ClinicalTrials.gov lists 26 registered studies with “Maridebart cafraglutide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07226765 | Maridebart Cafraglutide Versus Placebo in Adult Participants With Obstructive Sleep Apnea Not on Positive Airw | Phase 3 | active not recruiting | 2026-09-29 |
| NCT07441252 | A Trial to Evaluate Efficacy and Safety of Maridebart Cafraglutide in Adults Living With Elevated Liver Fat an | Phase 2 | active not recruiting | 2026-09-28 |
| NCT07037433 | Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerot | Phase 3 | recruiting | 2026-09-22 |
| NCT07832799 | Comparing the Extent to Which Two Maridebart Cafraglutide Drug Products Are Made Available in the Body After a | Phase 1 | not yet recruiting | 2026-09-22 |
| NCT07229157 | Effect of Maridebart Cafraglutide on the Heart's Electrical Activity | Phase 1 | completed | 2026-09-22 |
| NCT07225686 | Maridebart Cafraglutide Versus Placebo in Adult Participants With Obstructive Sleep Apnea on Positive Airway P | Phase 3 | active not recruiting | 2026-09-18 |
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- Trials1 registered study added on ClinicalTrials.gov (now 26).
- IdentifiersCross-linked to IUPHAR ligand 13316.
- TrialsClinicalTrials.gov snapshot added: 25 registered studies, highest phase 3.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Maridebart cafraglutide
What is Maridebart cafraglutide?+
Maridebart cafraglutide (MariTide, AMG 133) is an investigational antibody–peptide conjugate from Amgen: an antibody that antagonises the GIP receptor carrying two GLP-1 receptor agonist peptides. Dosed once monthly, it produced 12.3% to 16.2% weight loss at 52 weeks in a phase 2 trial in obesity versus 2.5% with placebo, and is in phase 3 as of September 2026.
What Canadian product status is recorded for Maridebart cafraglutide?+
Canadian product status for Maridebart cafraglutide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Maridebart cafraglutide?+
Maridebart cafraglutide is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.
What is MariTide?+
Maridebart cafraglutide (AMG 133), an Amgen antibody–peptide conjugate that blocks the GIP receptor and activates the GLP-1 receptor, dosed once monthly. It is in phase 3 trials for obesity.
How much weight loss did MariTide produce?+
In phase 2, −12.3% to −16.2% at 52 weeks in people with obesity (placebo −2.5%), and −8.4% to −12.3% in those with obesity and type 2 diabetes.
Is MariTide approved?+
No. It is investigational; the phase 3 MARITIME programme is under way as of September 2026.
How can MariTide and tirzepatide both work if one blocks GIP and the other activates it?+
That is an unresolved paradox in incretin biology; both approaches produce weight loss in humans, and reviews from 2026 treat the mechanism as an open question.
Related peptides
References & further reading
- 1.Jastreboff et al. (2025). Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial. New England Journal of Medicine
- 2.Véniant et al. (2024). A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nature Metabolism
- 3.Davies et al. (2026). The Paradox and Future of GLP-1/GIP Combination Therapies: Efficacy and Mechanisms. Annual Review of Nutrition
- 4.Davies et al. (2026). A metabolic comparison of GIPR agonism versus GIPR antagonism in male mice. Diabetes, Obesity and Metabolism
- 5.Son et al. (2026). Novel GLP-1-based Medications for Type 2 Diabetes and Obesity. Endocrine Reviews