MariTide Research Guide: Mechanism, Trials, and Regulatory Status

MariTide is engineered by conjugating a fully human monoclonal antibody that binds and blocks the GIP receptor to two GLP-1-analogue agonist peptides, joined by amino acid linkers. That makes it a bispecific antibody-peptide conjugate, not a single short peptide chain — closer in structure to a therapeutic antibody with peptide payloads attached than to a standalone research peptide.^[1]

The antibody backbone is also what supports MariTide's monthly dosing interval in its trials: antibody-based molecules are generally cleared from the body far more slowly than an unconjugated peptide, which is typically dosed daily or weekly. That slower clearance came with a more complex molecule to manufacture and characterise than a single peptide chain.^[1]

MariTide blocks the GIP receptor while activating the GLP-1 receptor — the opposite pairing from incretin medicines such as tirzepatide, which activate both receptors together. Preclinical work behind MariTide found that combining an anti-GIPR antibody with a GLP-1 receptor agonist produced greater weight loss in obese mice and cynomolgus monkeys than either mechanism alone, with a proposed mechanism in which the bispecific molecule binds both receptors on the same cell at once, amplifying a shared internal signalling pathway.^[1][3]

Amgen's own phase 2 publication describes MariTide plainly as a molecule that 'combines glucagon-like peptide-1 receptor agonism and glucose-dependent insulinotropic polypeptide receptor antagonism' for the treatment of obesity. Why two opposite pharmacological approaches to the same GIP receptor — agonism in some GLP-1/GIP medicines, antagonism in MariTide — can each be associated with weight loss is still an active research question; the receptor mechanisms across this wider medicine class, including tirzepatide's GIP agonism and retatrutide's third receptor, are set out in full in a dedicated overview rather than repeated here.^[2]

MariTide's first human data come from a first-in-human, randomised, double-blind, placebo-controlled trial in participants with obesity, run at three United States sites between August 2020 and November 2022 and registered as NCT04478708. It ran in two parts: single ascending doses (SAD) and multiple ascending doses (MAD). The published analysis reported on 75 of the 110 people enrolled across the trial's cohorts overall, covering five SAD cohorts (placebo and single doses from 21 to 840 mg) and three MAD cohorts.^[1][4]

Weight loss was dose-dependent in both the single- and multiple-dose cohorts, and in the multiple-ascending-dose cohorts it was maintained for up to 150 days after the final dose — consistent with the antibody scaffold's longer duration of action. The trial's authors described MariTide's phase 1 safety and tolerability profile as acceptable.^[1]

A phase 2, randomised, double-blind, placebo-controlled, dose-ranging trial (NCT05669599), published in 2025 in the New England Journal of Medicine, enrolled 592 participants in two cohorts: 465 with obesity, and 127 with obesity and type 2 diabetes. Obesity-cohort participants were assigned to one of several maridebart cafraglutide regimens — 140, 280 or 420 mg every four weeks without dose escalation; 420 mg every eight weeks; or 420 mg every four weeks preceded by a four- or twelve-week dose-escalation period — or to placebo. Participants with obesity and type 2 diabetes were assigned to 140, 280 or 420 mg every four weeks, or placebo. The primary endpoint was percent change in body weight from baseline to week 52.^[2]

In the obesity cohort, mean body weight fell by 12.3% to 16.2% across the maridebart cafraglutide groups by week 52, against 2.5% with placebo. In the obesity-with-diabetes cohort, weight fell by 8.4% to 12.3%, against 1.7% with placebo, alongside glycated haemoglobin (HbA1c) reductions of 1.2 to 1.6 percentage points, against 0.1 percentage points with placebo. The trial's authors reported that gastrointestinal adverse events were common but less frequent with dose escalation and a lower starting dose, and that no unexpected safety signals emerged.^[2]

Amgen's phase 3 programme for maridebart cafraglutide, named MARITIME, is built around two pivotal randomised, double-blind, placebo-controlled trials, each comparing three dose levels of maridebart cafraglutide against placebo over 72 weeks, with percent change in body weight from baseline as the primary endpoint. MARITIME-1 (NCT06858839) enrolled 3,853 participants with obesity or overweight who do not have type 2 diabetes; MARITIME-2 (NCT06858878) enrolled 1,105 participants with obesity or overweight who have type 2 diabetes.^[5][6]

As of September 2026, both trials are listed as active but no longer recruiting — enrollment is complete — with primary completion estimated for January 2027 and full study completion estimated for April 2027. Neither trial has reported results yet, so MariTide's weight-loss and safety record beyond 52 weeks is not yet published; this status can move, and is worth checking again after January 2027.^[5][6]

Amgen has also registered further phase 3 trials beyond obesity and type 2 diabetes: a cardiovascular-outcomes trial in people with atherosclerotic cardiovascular disease, and a trial in heart failure with preserved or mildly reduced ejection fraction, both in people with overweight or obesity. Both were still recruiting as of September 2026, with primary completion estimated for mid-2028.^[8][7]

Gastrointestinal effects are the most consistent finding across every published MariTide trial: nausea, vomiting, dyspepsia and related symptoms, increasing with dose in the phase 1 single- and multiple-ascending-dose cohorts. Phase 1 also recorded a small, non-dose-dependent rise in heart rate after dosing that stayed within a normal range, with neither tachycardia nor palpitations reported as adverse events, and no clinically meaningful change in blood pressure.^[1]

The phase 2 trial reported the same pattern at a larger scale: gastrointestinal adverse events were common overall but less frequent with a lower starting dose and gradual dose escalation, and its authors stated that no unexpected safety signals had emerged through 52 weeks.^[2]

As of September 2026, maridebart cafraglutide has no FDA or EMA approval anywhere; it remains an investigational compound, with its pivotal phase 3 trials still running toward a primary completion estimated for January 2027. The European Medicines Agency's database of authorised medicines lists no maridebart cafraglutide or MariTide product.^[5][6][9]

Peptyds does not supply maridebart cafraglutide or MariTide in any form. It supplies semaglutide, tirzepatide and retatrutide as lyophilised research peptides for in-vitro laboratory work only, each with batch documentation described on the quality page. MariTide is covered here because researchers search for the molecule directly, not because Peptyds sells it, and nothing in this article is guidance for personal use.