Maridebart cafraglutide
Amgen's monthly obesity drug, an antibody that blocks GIP carrying two GLP-1 peptides
Maridebart cafraglutide, known as MariTide, joins an antibody that blocks the GIP receptor to two GLP-1 peptides, so one monthly injection can do what weekly peptides do. In a 52-week phase 2 trial, weight fell 12% to 16% against 2.5% on placebo. It is in phase 3 and not approved.
What is it?
Maridebart cafraglutide is not a peptide in the usual sense. It is a full human antibody that blocks the receptor for GIP, a gut hormone, with two GLP-1 peptides chemically attached by linkers. The antibody gives it a long life in the blood, which is why it can be injected every four to eight weeks rather than weekly.
Its design runs against tirzepatide's. Tirzepatide activates the GIP receptor alongside GLP-1; MariTide blocks it. Both approaches produced weight loss in animals and people, and why opposite actions on the same receptor can both help remains an open scientific question that reviews discuss at length.
In the phase 2 trial published in 2025, 592 adults took one of several monthly or two-monthly doses or placebo for 52 weeks. In those with obesity, mean weight fell 12.3% to 16.2% against 2.5% on placebo; in those with obesity and type 2 diabetes it fell 8.4% to 12.3% against 1.7%, with HbA1c down 1.2 to 1.6 points. Gastrointestinal side effects were common, and less frequent when doses were escalated from a lower start.
A phase 3 programme, MARITIME, is under way in obesity and type 2 diabetes, with further trials in cardiovascular disease, heart failure and sleep apnoea, according to the developer; first phase 3 results are expected around 2027. It is not approved anywhere.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
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Published Research
These are the studies read from their PubMed abstracts on October 5, 2026.
Phase 2: 592 adults for 52 weeks
In the obesity cohort (465 people, mean BMI 37.9), weight fell 12.3% to 16.2% against 2.5% on placebo (intention-to-treat). In the obesity-with-diabetes cohort (127), weight fell 8.4% to 12.3% against 1.7%, and HbA1c 1.2 to 1.6 points. GI adverse events were common, less so with a lower starting dose; no unexpected safety signals.
First in people, and in animals
The molecule blocked GIPR and activated GLP-1R in cells and cut weight in obese mice and monkeys. In a phase 1 randomised, placebo-controlled study in people with obesity, it produced dose-dependent weight loss with acceptable tolerability, maintained up to 150 days after the last dose.
How the conjugate was designed
Amgen's medicinal-chemistry account: anti-GIPR antibodies conjugated to synthetic GLP-1 peptides gave prolonged exposure of the intact peptide and sustained weight loss with weekly dosing in obese mice and monkeys.
Antibody-peptide conjugates as a class
A review using maridebart cafraglutide as its main example: conjugating peptides to antibodies combines the antibody's long half-life with the peptide's activity, avoiding the rapid breakdown that limits peptides.
Side Effects & Contraindications
Reported Side Effects
From the phase 1 and phase 2 abstracts.
Contraindications & Cautions
There is no approved label, so no formal contraindications exist.
Legal Status
Investigational; not approved anywhere.
Frequently Asked Questions
?How much weight loss did MariTide produce?
In phase 2, 12.3% to 16.2% at 52 weeks in people with obesity, against 2.5% on placebo.
?How is it different from tirzepatide?
Tirzepatide activates the GIP receptor; maridebart cafraglutide blocks it, and its antibody lets it be injected monthly rather than weekly.
?When could it be approved?
Phase 3 results are expected around 2027, so any approval would come after that; it is not approved now.
References
- [pubmed] 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. PMID: 40549887.
- [pubmed] Véniant MM, et al. "A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings." Nat Metab, 2024;6(2):290-303. PMID: 38316982.
- [pubmed] Wu B, et al. "Discovery of AMG 133, a Glucose-Dependent Insulinotropic Polypeptide Receptor Antagonist and Glucagon-Like Peptide 1 Receptor Agonist Antibody-Drug Conjugate for the Treatment of Obesity." J Med Chem, 2026;69(8):9348-9362. PMID: 41941715.
- [pubmed] Yie J, et al. "Design and therapeutic rationale of antibody-peptide conjugates: insights from maridebart cafraglutide (AMG133) and emerging applications." Antib Ther, 2026;9(3):367-380. PMID: 42592044.
- [news-release] Amgen. "Amgen Announces Robust Weight Loss With MariTide in People Living With Obesity or Overweight at 52 Weeks in a Phase 2 Study." November 26, 2024.
- [clinicaltrials] NCT06858878 — Phase 3 MARITIME-2 trial in adults with type 2 diabetes and obesity/overweight. ClinicalTrials.gov.
Sources & Citations
Studies from their PubMed abstracts, read October 5, 2026; development status from the developer's announcements and ClinicalTrials.gov, as cited.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.