GLP-1

MariTide Explained: Amgen’s Monthly GIPR-Antagonist / GLP-1 Obesity Program

MariTide (maridebart cafraglutide / AMG 133) explained: mechanism vs semaglutide, tirzepatide, and retatrutide, Phase 2 trial status from opened sources, and why it is not a research-cake reconstitution job.

· 12 min read ·

⚕️ Medical Disclaimer: This article is for educational and informational purposes only. It does not constitute medical advice. Consult a qualified healthcare provider before using any peptide.

⚕️ Medical Disclaimer

⚕️ Medical Disclaimer: This article is for educational and informational purposes only. It does not constitute medical advice, a dosing protocol, or an endorsement of any investigational product. Consult a qualified healthcare provider for personal medical decisions.

What MariTide Actually Is

MariTide is Amgen’s brand name for maridebart cafraglutide (formerly AMG 133): a long-acting peptide–antibody conjugate built as a bispecific GLP-1 receptor agonist and glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist. That last word matters. Most of the obesity pipeline adds GIP activity. MariTide blocks the GIP receptor while agonizing GLP-1.

The construct is not a simple lyophilized research cake. Public development materials describe a monthly or less-frequent subcutaneous schedule under sponsor protocols — not a weekly twincretin pen you reconstitute like BPC-157. For identity and “do not invent a reconstitution chart” honesty, start with our MariTide peptide leaf.

This essay covers mechanism class, sourced Phase 2 status, and how MariTide differs from semaglutide, tirzepatide, and retatrutide. It does not duplicate leaf dosing math, because there is no honest DIY chart for an unverified vial labeled “MariTide.”

Mechanism: GLP-1 Agonism Plus GIP Receptor Antagonism

Amgen’s clinical framing is explicit: MariTide combines GLP-1 receptor agonism with GIP receptor antagonism in one long-acting conjugate. Amgen has also stated that human genetics work helped prioritize GIPR inhibition as a body-mass signal, and that preclinical work supported combining GLP-1 activation with GIP pathway inhibition over either alone.

Contrast that with the marketed and late-pipeline peers:

Semaglutide — GLP-1 receptor agonist only (Ozempic / Wegovy class).

Tirzepatide — dual GLP-1 and GIP receptor agonist (GIP agonism, not antagonism).

Retatrutide — investigational triple agonist at GLP-1, GIP, and glucagon receptors.

So if someone says “MariTide is just another GLP-1,” they flattened the story. Same incretin neighborhood. Opposite GIP story versus tirzepatide. See also our semaglutide vs tirzepatide vs retatrutide compare and the GLP-1 dose escalation guide for labeled weekly pens — those guides are not MariTide protocols.

Phase 2 Trial Status You Can Source

The Phase 2 obesity program is ClinicalTrials.gov NCT05669599. Full Phase 2 results were published in the New England Journal of Medicine (Jastreboff et al., 2025; PubMed PMID 40549887) under the nonproprietary name maridebart cafraglutide.

Design snapshot from that paper: a double-blind, randomized, placebo-controlled, dose-ranging Phase 2 trial with 592 participants across an obesity cohort and an obesity-with-type-2-diabetes cohort. Primary endpoint was percent change in body weight from baseline to week 52.

In the obesity cohort (465 participants), mean percent weight change at week 52 on the treatment-policy (intention-to-treat) estimand ranged from −12.3% to −16.2% with maridebart cafraglutide versus −2.5% with placebo. In the obesity–diabetes cohort (127 participants), the same estimand ranged from −8.4% to −12.3% versus −1.7% placebo. Mean glycated hemoglobin change in the diabetes cohort was −1.2 to −1.6 percentage points on active drug versus +0.1 on placebo.

Trial arms in that paper included subcutaneous doses of 140, 280, or 420 mg every 4 weeks (with and without dose-escalation schemes in some obesity arms), plus a 420 mg every-8-weeks arm without escalation in the obesity cohort. Those milligrams are study conditions in a sponsored antibody–peptide conjugate program — not a gray-market reconstitution table.

Amgen’s June 23, 2025 ADA scientific-sessions press release summarized Part 1 Phase 2 results using an efficacy estimand of up to about 20% average weight loss without type 2 diabetes (versus about 2.6% placebo) and up to about 17% with type 2 diabetes (versus about 1.4% placebo), and noted weight loss had not plateaued by 52 weeks in that framing. Prefer the NEJM treatment-policy numbers when you need the intention-to-treat lens; prefer Amgen’s estimand language when quoting Amgen.

Gastrointestinal adverse events were common in the NEJM report, less frequent with dose escalation and a lower starting dose, with no unexpected safety signals called out in the abstract. That is Phase 2 tolerability context, not a community side-effect folklore sheet.

How It Differs From Semaglutide, Tirzepatide, and Retatrutide

Schedule class: MariTide’s public program is monthly or less frequent. Semaglutide and tirzepatide obesity pens are once weekly. Retatrutide’s Phase 2 obesity work was also weekly-class investigational. Do not mix schedules across molecules.

Receptor map: Semaglutide = GLP-1 only. Tirzepatide = GLP-1 + GIP agonism. Retatrutide = GLP-1 + GIP + glucagon agonism. MariTide = GLP-1 agonism + GIPR antagonism. Calling all of them “GLP-1s” is marketing shorthand, not pharmacology.

Product form: Wegovy/Ozempic and Zepbound/Mounjaro are finished labeled pens in the United States. Retatrutide and MariTide are investigational programs on this site’s leaf dates — not interchangeable research cakes. If a vendor sells “MariTide,” treat identity as unverified until a COA and supply chain say otherwise.

For pipeline cousins that add glucagon instead of blocking GIP, see our mazdutide and pemvidutide leaves and the related trial essays — dual GLP-1/glucagon is a different design bet than MariTide’s GIPR block.

What This Site Will Not Do

We will not publish a DIY reconstitution chart for an antibody–peptide conjugate you cannot authenticate. We will not treat Phase 2 milligrams as a home protocol. We will not claim FDA approval that does not exist. Obesity care belongs with a clinician and, when available, labeled products — not a research-chem SKU with a borrowed Amgen name.

If you need weekly incretin math for products that actually have pens and published titration steps, use the CalcMyPeptide GLP-1 scheduler and the peptide leaves for semaglutide, tirzepatide, and retatrutide. Keep MariTide in the “pipeline literacy” column until a finished label exists.

Frequently Asked Questions

Is MariTide the same as tirzepatide?
No. Tirzepatide agonizes GIP and GLP-1 receptors. MariTide (maridebart cafraglutide) agonizes GLP-1 and antagonizes the GIP receptor. Opposite GIP pharmacology.
Is MariTide FDA-approved?
Not as a finished US obesity pen on the sources we opened. Phase 2 obesity data (NCT05669599; NEJM 2025) are investigational program results, not a label.
What weight-loss numbers were reported?
In the NEJM Phase 2 report, treatment-policy estimand weight change at 52 weeks was about −12.3% to −16.2% versus −2.5% placebo in the obesity cohort, and −8.4% to −12.3% versus −1.7% in the obesity–diabetes cohort. Amgen’s efficacy-estimand press framing cited higher averages. Those are trial statistics, not a home dose target.
Can I reconstitute a research vial labeled MariTide?
You should not treat an unverified cake as AMG 133. See the MariTide leaf — there is no honest reconstitution chart for that SKU class.
How is the schedule different from Wegovy or Zepbound?
MariTide’s public program is monthly or less frequent. Semaglutide and tirzepatide obesity pens are weekly. Do not copy schedules across molecules.

📖 References

  1. Jastreboff AM, et al. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial.” N Engl J Med (2025). PMID: 40549887

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Citations

  1. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial — Jastreboff AM, et al.. N Engl J Med (2025) · PMID 40549887

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