MariTide

What is MariTide?

MariTide (maridebart cafraglutide, AMG 133) is Amgen's first-in-class bispecific antibody-peptide conjugate for obesity. It combines a fully human anti-GIPR monoclonal antagonist antibody with two GLP-1 agonist peptide arms — creating a single molecule that activates the GLP-1 receptor while simultaneously blocking the GIP receptor. This is the opposite direction from tirzepatide (which agonizes both), based on human genetics data showing loss-of-function GIPR variants are associated with lower BMI. The antibody scaffold gives MariTide a long half-life — about 14 to 16 days for the intact drug and 21 to 24 days for total antibody in Phase 1 — which allows once-monthly dosing, with every-8-week and quarterly maintenance schedules now in trials. Amgen says patients may stay on it with as few as 4 or 6 doses a year, versus 52 for weekly agents. Phase 2 NEJM (published online June 2025, print September 2025; 592 participants, 52 weeks): mean weight loss of up to 16.2% by intention-to-treat (treatment-policy estimand) versus 2.5% on placebo, and up to 19.9% by the efficacy estimand, which estimates results as if everyone stayed on the drug, versus 2.6% on placebo. Weight loss was maintained up to 150 days post-treatment in Phase 1. The two Phase 3 weight trials, MARITIME-1 (3,853 adults without diabetes) and MARITIME-2 (1,105 adults with type 2 diabetes), began in March 2025; ClinicalTrials.gov lists primary completion in January 2027, so topline results would come after that.

What MariTide Is Investigated For

MariTide is Amgen's investigational once-monthly bispecific antibody-peptide conjugate for obesity and type 2 diabetes, combining GLP-1 receptor agonism with GIP receptor antagonism — a mechanistic inversion of tirzepatide's dual agonism, motivated by human genetics data linking loss-of-function GIPR variants to lower BMI. The strongest evidence is the 2025 NEJM Phase 2 trial (n=592, 52 weeks) showing up to 16.2% mean weight loss by intention-to-treat and up to 19.9% by the efficacy estimand (2.5% and 2.6% on placebo), with no observed plateau at trial end, and HbA1c reductions of 1.2–1.6 percentage points in the obesity+T2D cohort. The antibody scaffold produces a ~21-day half-life enabling monthly (or Q8W) dosing — 12 injections per year vs. 52 for weekly agents — and in a small Phase 1 group, weight was still well below baseline 150 days after the last dose (no head-to-head rebound comparison with weekly GLP-1 drugs exists). The honest caveats are that MariTide is not FDA-approved, the first Phase 3 MARITIME weight trials list primary completion in January 2027, cross-trial comparisons with tirzepatide are not head-to-head, and monthly dosing creates a tolerability asymmetry: GI side effects cannot be quickly dose-reduced given the long half-life. The antibody-peptide format also cannot be reproduced by standard peptide synthesis, so any product sold as 'MariTide' outside Amgen's trials is not MariTide.

History & Discovery

MariTide — originally known by its internal Amgen code AMG 133 and formally named maridebart cafraglutide — originated in Amgen's metabolic biologics program in the late 2010s and early 2020s. The mechanistic rationale leaned heavily on human genetics: large-scale sequencing, including work by Amgen's deCODE Genetics in Iceland, had linked loss-of-function variants in the GIPR gene to lower BMI, suggesting that pharmacologic GIPR antagonism, rather than agonism, might be weight-reducing. Amgen chose to test this in the most direct way available — by engineering a bispecific molecule combining a fully human GIPR-antagonist monoclonal antibody with GLP-1-agonist peptide arms attached via amino acid linkers. The format is unusual in obesity: antibody-derived half-life extension already existed among incretin drugs (dulaglutide is a GLP-1 peptide fused to an antibody Fc fragment), but MariTide was the first to use a full, target-binding antibody that also blocks a second receptor. Phase 1 results published in Nature Metabolism in early 2024 (Véniant et al.) demonstrated dose-dependent weight loss and a remarkably prolonged post-treatment effect, with weight loss maintained up to 150 days after the last dose. The Phase 2 NEJM paper was published online in June 2025 alongside the ADA Scientific Sessions (print September 2025; n=592, 52 weeks) and reported mean weight loss of up to 16.2% by intention-to-treat and up to 19.9% by the efficacy estimand, with curves still sloping downward at trial end — no plateau observed. The Phase 3 MARITIME program launched in March 2025 with MARITIME-1 and MARITIME-2 targeting obesity and obesity+T2D respectively, followed in mid-to-late 2025 by MARITIME-HF, MARITIME-CV, and two obstructive sleep apnea trials. As of the site's current revision, MariTide is not FDA-approved.

How It Works

MariTide is a molecular hybrid — part antibody, part peptide. The antibody part blocks the GIP receptor, and two peptide arms activate the GLP-1 receptor. The antibody gives MariTide a very long half-life (roughly 2 to 3 weeks), which is why it only needs to be injected once a month instead of weekly like Ozempic or Zepbound. When you stop, it slowly washes out over several months, which may soften the dramatic weight regain that happens after stopping weekly GLP-1s.

MariTide (maridebart cafraglutide) is a bispecific antibody-peptide conjugate combining one fully human IgG1-kappa anti-GIPR antagonist antibody (the 'maridebart' part of the name) with two identical GLP-1 analogue peptides (the 'cafraglutide' part), each attached through an 18-amino-acid glycine-serine linker to an engineered cysteine in the antibody's Fc region. GLP-1R agonism drives appetite suppression, slowed gastric emptying, and glucose-dependent insulin secretion. GIPR antagonism targets the paradoxical human genetics signal (loss-of-function GIPR variants → lower BMI). The antibody scaffold confers a long half-life (about 14 to 16 days intact, 21 to 24 days total antibody) (vs semaglutide ~1 week, tirzepatide ~5 days), enabling once-monthly or even Q8W dosing. Phase 2 (NCT05669599, 592 participants, 52 weeks, NEJM 2025): obesity cohort weight loss −12.3% to −16.2% (treatment-policy; placebo −2.5%) and −16.3% to −19.9% (efficacy estimand; placebo −2.6%); obesity plus type 2 diabetes cohort −8.4% to −12.3% (treatment-policy) and −12.1% to −17.0% (efficacy), with HbA1c reductions of −1.2 to −1.6 points (treatment-policy) and up to −2.2 points (efficacy). No weight-loss plateau observed at 52 weeks. Dose escalation (4-week or 12-week) substantially reduced GI AEs. Phase 1 showed weight loss maintained up to 150 days post-last-dose.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about MariTide:

• 01Bone health — GIP receptors are present on bone cells and an early Phase 1 data table raised a bone-density question; Amgen reports no association in Phase 2, but bone-density and fracture data from the 72-week Phase 3 trials have not been reported.
• 02Maintenance dosing — Amgen's summary of Phase 2 Part 2 says most participants kept their weight off for a second year on lower monthly or quarterly doses, but these data come from a selected group (at least 15% weight loss) and are not peer-reviewed; the MARITIME extension trials will test this at scale.
• 03Type 2 diabetes dose-finding — a dedicated 24-week Phase 2 trial (NCT06660173, 409 adults) has finished its primary timepoint, and Amgen describes the HbA1c and weight results as robust but has not released the numbers.
• 04Phase 3 efficacy and safety readouts — MARITIME-1 and MARITIME-2 are fully enrolled and in follow-up, with primary completion listed for January 2027 on ClinicalTrials.gov; the weight-loss plateau beyond 52 weeks has not been characterized.
• 05Cardiovascular outcomes — MARITIME-CV is designed to test MACE reduction; until it reports, cardiovascular benefit is inferred from class effects rather than directly established for MariTide.
• 06Direct head-to-head vs. tirzepatide and semaglutide — cross-trial comparisons favor MariTide on dosing convenience and trajectory, but no head-to-head randomized comparison has been reported.
• 07Long-term immunogenicity — anti-drug antibody development over 2+ years of monthly dosing needs extended follow-up to establish durability of efficacy and any safety signals.
• 08Real-world management of monthly dosing — tolerability-driven dose reduction is logistically harder with a monthly agent than with weekly peptides; whether this changes discontinuation patterns in practice is untested outside trial settings.
• 09Washout and weight-regain kinetics — Phase 1 showed preservation up to 150 days post-dose, but whether the softer washout translates into different 12–24 month regain curves vs. weekly GLP-1s is a question for post-Phase 3 observational data.
• 10The biology of GIPR antagonism itself — why pharmacologic GIPR antagonism and chronic GIPR agonism both produce weight loss (the 'GIPR paradox') is an active research question with implications beyond MariTide.

Forms & Administration

MariTide is administered as a once-monthly (Q4W) or once-every-8-weeks (Q8W) subcutaneous injection. Phase 2 tested 140 mg to 420 mg (escalation arms started at 70 mg); Phase 3 starts at 21 mg and steps through 35 mg and 70 mg over 8 weeks. Currently only available through clinical trials.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

MariTide is not FDA-approved for any indication as of the site's current revision. These dose ranges reflect published trial protocols and are not prescriptions. Access outside of enrollment in Amgen's MARITIME program or related clinical trials is not legitimate.

Timeline of Effects

Common Questions

Who MariTide Is NOT For

Drug & Supplement Interactions

No FDA-labeled interaction profile exists for MariTide because the drug is not approved. The framework is extrapolated from the GLP-1 class and from general antibody-biologic considerations. The most clinically relevant GLP-1-class interactions — hypoglycemia risk with insulin or sulfonylureas, altered oral drug absorption from delayed gastric emptying — apply here, with the important caveat that MariTide's monthly dosing interval creates an unusual pharmacokinetic landscape: drug exposure is steady rather than pulsatile, which may change how interactions manifest compared with weekly peptides. Narrow-therapeutic-index oral agents (warfarin, levothyroxine, certain antiepileptics) warrant the same attention they receive with other GLP-1s. The GIPR-antagonism component is pharmacologically novel in clinical use; there are no established interaction datasets for it, and the effect on lipid handling, postprandial triglycerides, and adipose biology in the context of co-administered metabolic therapies is being characterized in MARITIME. Immunogenicity — anti-drug antibody development — is the one interaction domain distinct from small-molecule peptides and requires monitoring over extended use.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions