Metabolic & GLP-1Evidence B2 cited

MariTide

aka MariTide · Maridebart cafraglutide · AMG 133

GLP-1 agonist / GIP ANTAGONIST antibody-peptide conjugate. Monthly dosing. Novel mechanism.

CAS

2760218-55-9

Sequence

Read this before quoting the sequence

MariTide is maridebart cafraglutide (AMG 133), a peptide-antibody conjugate, not a peptide, so no single sequence applies. Per the FDA GSRS record (UNII Z24U3U73HN, INN 12602): a fully human anti-GIPR IgG1 monoclonal antibody comprising two 450-residue heavy chains (beginning QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGEGLEWVAA...) and two 214-residue kappa light chains (beginning EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ...), with C-terminal lysine clipping and N-terminal pyroglutamate; engineered Cys275 on each heavy chain is conjugated by thioether linkage to a GLP-1 analogue peptide (GLP-1 7-35 with Ala8>2-methylalanine, Val16>Tyr, Gly22>Glu) via an 18-residue diglycyl-tris(tetraglycyl-seryl)-lysinamide linker. Two GLP-1 analogue peptides per antibody. Full chains are not reproduced here.

Source ↗

Mechanism of action

Bispecific molecule (maridebart cafraglutide): a GIP-receptor antagonist antibody conjugated to two GLP-1 receptor agonist peptides. Long half-life supports once-monthly dosing; combines GLP-1 agonism with GIP-receptor blockade for weight loss.

What the evidence actually shows

Grade B

Phase 2 ongoing. Monthly injection. GIPR antagonism may reduce nausea.

Regulatory status

Status

Investigational. No marketing authorisation anywhere; not listed in Drugs@FDA or the EMA medicines register. Developed by Amgen. INN maridebart cafraglutide (INN list number 12602); FDA UNII Z24U3U73HN.

Clinical stage

Phase 3. The MARITIME programme includes NCT06858839 (obesity without type 2 diabetes, phase 3, started March 2025), NCT06858878 (obesity with type 2 diabetes, phase 3), NCT06987695 (Japan, phase 3) and NCT07225686 (obstructive sleep apnoea, phase 3, started December 2025). Phase 2 obesity results published in NEJM in 2025.

WADA

Not named on the 2026 WADA Prohibited List; GLP-1 receptor agonists and GIPR antagonists do not appear in any section of that list.

Source ↗

Dosing — what backs each figure

MariTide (maridebart cafraglutide) is a clinical-stage GLP-1 receptor agonist / GIP receptor antagonist peptide-antibody conjugate with published phase 2 dosing of 140, 280 or 420 mg subcutaneously every 4 weeks (or 420 mg every 8 weeks), with or without 4- or 12-week dose escalation. It is not approved anywhere; phase 3 trials are ongoing (e.g. NCT06858839, NCT06987695, NCT07226765).

ClinicalApproved labelling or a published human trial

Maridebart cafraglutide subcutaneously at 140 mg, 280 mg or 420 mg every 4 weeks without dose escalation; 420 mg every 8 weeks without dose escalation; 420 mg every 4 weeks with 4-week dose escalation; 420 mg every 4 weeks with 12-week dose escalation; or placebo. Phase 2, double-blind, randomised, placebo-controlled dose-ranging trial with 11 groups across two cohorts
Adults with obesity, and a second cohort of adults with obesity and type 2 diabetes · subcutaneous
Jastreboff AM et al. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial. N Engl J Med. 2025;393(9):843-857 (ClinicalTrials.gov NCT05669599) ↗

No established human dose

No approved label or completed human trial establishes a dosing regimen for this compound. Anything presented as a standard protocol for it — anywhere — is someone's convention rather than a finding.

Handling and storage

No compound-specific stability data exists

MariTide is investigational and has no approved label, so no public storage specification exists. No compound-specific stability data was located in any regulatory or peer-reviewed source. General peptide handling still applies — reconstitute gently, keep it cold, keep it dark — but any specific figure you see quoted for this compound elsewhere is someone's assumption, not a measurement.

→ Reconstitution walkthrough → Reconstitution calculator

Safety

References (2)

Jastreboff AM, Ryan DH, Bays HE, Ebeling PR, Mackowski MG, Philipose N, Ross L, Liu Y, Burns CE, Abbasi SA, Pannacciulli N; MariTide Phase 2 Obesity Trial Investigators (2025) Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial ↗
The New England Journal of MedicinePMID 40549887DOI
Phase 2 dose-ranging trial (NCT05669599) in 592 participants: subcutaneous maridebart cafraglutide 140, 280 or 420 mg every 4 weeks (or 420 mg every 8 weeks) gave mean body-weight change at week 52 of -12.3% to -16.2% in the obesity cohort versus -2.5% with placebo.
Veniant MM, 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 MetabolismPMID 38316982DOI
Describes AMG 133 as a bispecific molecule made by conjugating a fully human anti-GIPR antagonist antibody to two GLP-1 analogue agonist peptides via amino acid linkers, and reports weight reduction in obese mice, cynomolgus monkeys and a phase 1 study.

Data provenance

Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.

Could not verify
molecularFormula, molecularWeight, pubchemCid, sequence.oneLetter, sequence.threeLetter, storage.lyophilized, storage.reconstituted, storage.lightSensitive, reconstitution.solvent

Research use only

This profile is educational reference material. It is not medical advice, not a prescription, and not an endorsement of self-administration. Compounds discussed here are research chemicals and most are not approved for human therapeutic use.

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