{"id":"maridebart-cafraglutide","name":"Maridebart cafraglutide","aliases":["MariTide","AMG 133","MariTide peptide"],"url":"https://lyoresearch.com/compounds/maridebart-cafraglutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Maridebart cafraglutide, or MariTide, is an antibody that blocks the GIP receptor with two GLP-1-agonist peptides attached, injected once a month. In a 592-person phase 2 trial published in the New England Journal of Medicine in 2025, people with obesity lost 12–16% at 52 weeks against 2.5% on placebo. Gut side effects were common, less so with dose escalation. Phase 3 trials are running; it is not approved anywhere.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"1 phase 2 RCT (n=592); phase 3 running","regulatory_status":"Investigational (phase 3)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A monoclonal antibody conjugated to two GLP-1 peptides — no small-molecule record"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, every 4 weeks","half_life":"About 14–16 days for the intact molecule (21–24 days total)","licensed_regimen":null,"product":null,"source":{"title":"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;6:290–303","url":"https://www.nature.com/articles/s42255-023-00966-w"}},"outcomes":[{"outcome":"Body weight (obesity)","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 2 RCT (465 in the obesity cohort, 52 wk)","evidence":"Six dosing regimens of 140–420 mg every four or eight weeks. Intention-to-treat loss ranged from 12.3% to 16.2% against 2.5% on placebo. In the 127-person diabetes cohort, 8.4–12.3% against 1.7%.","references":[{"citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}],"verbatim":{"text":"In the obesity cohort (465 participants; female sex, 63%; mean age, 47.9 years; mean body-mass index [BMI, the weight in kilograms divided by the square of the height in meters], 37.9), the mean percent change in body weight from baseline to week 52 on the basis of the treatment policy estimand (intention-to-treat approach) ranged from -12.3% (95% confidence interval [CI], -15.0 to -9.7) to -16.2% (95% CI, -18.9 to -13.5) with maridebart cafraglutide, as compared with -2.5% (95% CI, -4.2 to -0.7) with placebo.","citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}},{"outcome":"Blood glucose (HbA1c) in type 2 diabetes","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Same RCT, diabetes cohort (n=127)","evidence":"HbA1c fell 1.2–1.6 points against 0.1 on placebo.","references":[{"citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}],"verbatim":{"text":"The mean change in the glycated hemoglobin level on the basis of the treatment policy estimand in this cohort was -1.2 to -1.6 percentage points in the maridebart cafraglutide groups and 0.1 percentage points in the placebo group.","citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}},{"outcome":"GI side effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":true,"human_studies":"Same RCT","evidence":"Nausea and vomiting were frequent, particularly without dose escalation; the regimens that started low and stepped up were better tolerated, which is why phase 3 uses escalation.","references":[{"citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}],"verbatim":{"text":"Gastrointestinal adverse events were common with maridebart cafraglutide, although less frequent with dose escalation and a lower starting dose.","citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational."},{"region":"United States","status":"Not approved","note":"Investigational; phase 3 running. Products sold as 'MariTide' online are not the trial drug and cannot be, given the manufacturing involved."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so S0 (non-approved substances)."}],"faq":[{"q":"Is MariTide a peptide?","a":"Partly. Two GLP-1 peptides are attached to an antibody. The antibody gives it the month-long half-life; the peptides do the metabolic work."},{"q":"How does MariTide compare with tirzepatide?","a":"Lower weight loss so far (up to 16% at 52 weeks versus tirzepatide's 21% at 72), given monthly rather than weekly, and with the opposite action at the GIP receptor. No direct comparison exists."},{"q":"Can you buy MariTide?","a":"No. It is an investigational antibody conjugate made by Amgen; nothing sold online under the name is the real molecule."}],"references":[{"cite":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/","note":"592 enrolled; obesity and obesity-diabetes cohorts; 52 weeks. NCT05669599."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication from the NEJM phase 2. Grade B."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}