Maridebart Cafraglutide (MariTide / AMG 133)

Maridebart cafraglutide (MariTide) is a real, investigational obesity drug from Amgen built on a genuinely different modality from every other GLP-1-family peptide on this site: a monoclonal antibody against the GIP receptor, chemically conjugated to two GLP-1 receptor agonist peptides, dosed once monthly rather than weekly. Its published Phase 2 trial found up to 20% weight loss — but also a real, disclosed gastrointestinal tolerability problem serious enough that Amgen redesigned its Phase 3 dosing strategy in direct response. It is not approved anywhere, and Phase 3 has not yet read out.

What it is: a peptide-antibody conjugate, not a plain peptide

Every dual-agonist obesity peptide covered elsewhere on this site — tirzepatide, survodutide, mazdutide, this site's own pemvidutide page — is a single synthetic peptide chain. Maridebart cafraglutide (Amgen's internal code AMG 133, brand-in-development name MariTide) is built differently: a fully human monoclonal antibody that binds and blocks the GIP receptor (acting as an antagonist, the opposite of tirzepatide's GIP-receptor agonism), with two GLP-1 receptor agonist peptide molecules chemically attached to it through amino-acid linkers. The antibody component is what gives the whole conjugate a long enough half-life to be dosed once monthly rather than once weekly — the least frequent dosing schedule of any investigational or approved drug in this drug class on this site.

The Phase 1 and Phase 2 evidence

A Phase 1 trial (NCT04478708) reported dose-dependent weight loss with an acceptable safety and tolerability profile, mostly mild gastrointestinal adverse events (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, PMID 38316982). The Phase 2 trial that followed was published in full (Jastreboff AM, Ryan DH, Bays HE, et al., "Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial," N Engl J Med 2025;393:843-857, PMID 40549887, published 23 June 2025): participants with obesity or overweight without type 2 diabetes lost up to roughly 20% of body weight, and those with type 2 diabetes up to roughly 17%, over the trial's dosing period — weight loss in the same range reported for some of the most effective approved GLP-1-family drugs, achieved with a monthly rather than weekly injection.

The real tolerability problem, and how Amgen responded

The same Phase 2 program also generated a genuine, disclosed problem. Data presented at the American Diabetes Association's 85th Scientific Sessions in June 2025 showed vomiting in roughly a quarter of participants in some dose-escalation arms (24.4% and 22.5% in the two escalation regimens studied), and in arms without dose escalation, gastrointestinal adverse events drove enough discontinuations that trade press covered it as a "high discontinuation" signal. Amgen's own reporting showed the dose-escalation arms performed better than fixed, non-escalated high-dose arms on this measure. In direct response, Amgen redesigned its Phase 3 MARITIME program around a slower titration: an initial 21mg starting dose, stepped up to 35mg and then 70mg over an eight-week escalation period, rather than starting patients on a high fixed dose.

What's still unresolved

Maridebart cafraglutide is not approved anywhere, and no regulatory filing has been submitted as of this review. The redesigned Phase 3 program — MARITIME-1 in obesity/overweight, MARITIME-2 in type 2 diabetes with overweight or obesity, and additional planned studies in cardiovascular disease, heart failure, chronic kidney disease and obstructive sleep apnea — was ongoing but had not read out as of this review. Whether the slower, three-step dose-escalation schedule actually resolves the vomiting and discontinuation problem seen in Phase 2, at Phase 3 scale, is a real open question rather than something already demonstrated.