Body journey · 7 steps

Inside the body with Maridebart cafraglutide (MariTide)

MariTide is an experimental weight-loss medicine from Amgen. It is built from an antibody that blocks one gut-hormone receptor (GIP) and two small peptides that switch on another (GLP-1). It stays in the body a long time: about three weeks after a dose, roughly half of it is still in the blood. That is why it was tested once a month. It is not approved anywhere yet. Big phase 3 trials are still running.

Scroll to follow it through the body

01Skin
Given as a slow-release injection under the skin
In the trials, the medicine was injected under the skin about once a month. It then moves slowly into the blood.
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Phase 1 and phase 2 studies used subcutaneous administration every 4 weeks; one phase 2 arm used every 8 weeks without dose escalation. Amgen states that the long-acting design supports starting with monthly dosing and staying on treatment with as few as 4 or 6 doses per year, and its phase 3 switch and extension studies test every-8-week and quarterly schedules. This is a development plan, not an approved regimen.[src][src]
02Bloodstream
An antibody carrier keeps it in the blood for weeks
Small peptide medicines are usually cleared from the blood within hours or days. Here the peptides are attached to an antibody, which the body clears very slowly. The half-life (the time for half of it to leave the blood) is about 21 days.
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Conjugation of two GLP-1 analogue peptides to an IgG1 gave a mean half-life of about 21 days in the phase 1 study (about 21 to 24 days for total drug, 14 to 16 days for intact conjugate in single-dose cohorts), compared with about 1 week for semaglutide. In mice and monkeys, assays distinguished 'intact' conjugate (at least one peptide still attached) from 'total' antibody; intact conjugate cleared faster, indicating that peptide loss from the antibody contributes to clearance of active drug (animal data). The J Med Chem discovery paper reports that conjugating GLP-1 peptides to anti-GIPR antibodies gave markedly prolonged systemic exposure of the structurally intact GLP-1 peptide.[src][src][src]
03Elsewhere
The antibody part blocks GIP receptors
GIP is a gut hormone. The antibody sticks to the GIP receptor and stops GIP from switching it on. Why this helps with weight is still being worked out, and some scientists are debating it.
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The antibody is a GIPR antagonist: in cell cAMP assays it inhibited GIP signalling through human GIPR (IC50 42.4 nM) and cynomolgus GIPR (26.5 nM), but was more than 20-fold weaker at rat GIPR and did not fully block mouse GIPR, so a mouse-specific surrogate antibody conjugate was used for mouse studies. The stated rationale is human genome-wide association data linking the GIPR locus (and lower GIPR function) to body weight, protection of GIPR knockout mice from diet-induced obesity, and earlier Amgen work in which GIPR antagonism combined with GLP-1R agonism reduced body weight synergistically in obese mice and monkeys (animal data). The phase 1 authors state it is unclear how to reconcile this with the added weight loss seen with GIPR/GLP-1R dual agonists, and that the precise mechanism in humans is not known.[src][src]
04Brain
The peptides switch on GLP-1 receptors, which is thought to turn down appetite
The two small peptides copy GLP-1, a gut hormone that helps signal fullness. Other GLP-1 medicines turn down appetite, partly through brain areas that control hunger. MariTide is a very large molecule that probably cannot cross into most of the brain, so it may act on nerve areas that sit outside the brain's barrier. That idea has only been looked at in animals. For MariTide, the proven part is the weight loss in trials.
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The conjugate is a full agonist of human GLP-1R in cAMP assays (EC50 24.4 pM). For the approved GLP-1R agonist semaglutide, the label states that GLP-1 receptors are present in brain areas involved in appetite regulation and that, in animals, semaglutide reached and activated neurons in those regions; rodent work shows it acts via circumventricular organs without crossing the blood-brain barrier. In adults with obesity, semaglutide reduced appetite ratings and ad libitum energy intake. For maridebart cafraglutide, the phase 1 authors note that as a large antibody conjugate it likely does not cross the blood-brain barrier, and that reduced food intake in obese mice (surrogate) and monkeys may reflect peripheral effects or receptors outside the barrier such as in the area postrema (animal data). No appetite or energy-intake study of MariTide in humans was found.[src][src][src][src]
05Pancreas
Blood sugar falls in people with type 2 diabetes
GLP-1 receptors on pancreas cells help the body release insulin when blood sugar is high. In the trial in people with diabetes, average blood sugar fell clearly.
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In the obesity-diabetes cohort of the phase 2 trial, mean HbA1c fell by 1.2 to 1.6 percentage points in maridebart cafraglutide groups versus 0.1 with placebo at week 52 (treatment-policy estimand). In phase 1 participants with obesity, fasting glucose fell dose-dependently. The split between weight-dependent and direct pancreatic effects was not resolved in these trials.[src][src]
06Stomach
Food may leave the stomach more slowly
GLP-1 medicines can slow how fast the stomach empties. Amgen has finished a study measuring this for MariTide, but no results had been published as of September 2026.
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The semaglutide label states that semaglutide delays gastric emptying; however, in a 20-week study of semaglutide in adults with obesity there was no evidence of delayed gastric emptying at week 20 by paracetamol absorption, so the size of this effect with long-term dosing is uncertain. A dedicated phase 1 gastric emptying study of AMG 133 (NCT07429032, paracetamol absorption endpoints) is listed as completed, but no results were found as of 2026-09-29, so this step is inferred from class pharmacology and unconfirmed for this molecule. Nausea and vomiting were its most common adverse events.[src][src][src][src]
07Fat tissue
Body weight comes down over months
In a one-year trial, adults with obesity who took MariTide lost on average about 12 to 16 percent of their body weight, compared with about 2.5 percent on placebo. People who also had type 2 diabetes lost about 8 to 12 percent, compared with about 2 percent on placebo. Weight had not levelled off at one year, and results from longer trials are not known yet.
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Phase 2 obesity cohort (n=465): mean weight change -12.3% to -16.2% at week 52 (treatment-policy estimand) versus -2.5% placebo; Amgen reports up to about 20% on the efficacy estimand versus 2.6% placebo, with weight loss not having plateaued by 52 weeks. Obesity-diabetes cohort (n=127): -8.4% to -12.3% versus -1.7% placebo (treatment-policy estimand). In phase 1 multiple-dose cohorts, weight loss was maintained for up to 150 days after the last dose. A mouse surrogate conjugate reduced body weight in obese mice, and AMG 133 reduced body weight in obese cynomolgus monkeys (animal data). Durability beyond 52 weeks is being studied in phase 3.[src][src][src]