Evidence Grade E — Very limited evidence. 5 published studies. 12 registered clinical trials.
Medically reviewed by a licensed medical professional
MariTide is a large antibody-peptide hybrid from Amgen that takes the opposite approach to tirzepatide: where tirzepatide activates the GIP receptor, MariTide blocks it, while simultaneously activating GLP-1 receptors. Its most notable feature is monthly dosing — the longest interval of any obesity treatment in development. Weight loss appeared to continue beyond 52 weeks without plateauing.
MariTide is also known by these brand and alternate names:
5 published studies: 3 human, 1 animal, 0 in-vitro, 3 reviews
MariTide is in Phase II/III development (not yet approved). Phase II results (592 patients, 52 weeks) showed 16–20% weight loss across doses. Body composition analysis showed 26–37% fat mass reduction with 8–13% lean mass reduction. Notably, weight loss appeared to continue beyond the 52-week treatment period without plateau.
MariTide's monthly dosing would be a significant convenience advantage if efficacy is confirmed in Phase III. The ongoing weight loss trajectory without plateau is particularly interesting and distinguishes it from some GLP-1 agonists where weight loss plateaus. Amgen is conducting Phase III trials.
MariTide simultaneously activates GLP-1 receptors (via two attached peptides) while blocking GIP receptors (via the antibody component). This is the opposite GIP approach from tirzepatide, which activates GIP. Human genetic data support both approaches — GIP receptor loss-of-function variants are associated with lower BMI — but they may work through different metabolic mechanisms. The antibody backbone provides a long half-life enabling monthly dosing.
Phase II results (592 patients, 52 weeks) showed 16-20% weight loss with monthly injections. Body composition analysis showed 26-37% fat mass reduction while limiting lean mass loss to 9-12% — a favourable ratio. The ongoing weight loss trajectory without plateau is particularly interesting and distinguishes MariTide from some GLP-1 drugs where weight loss levels off. Phase III trials (the MARITIME programme) have been initiated, with results expected around 2027. Additional trials are planned for cardiovascular disease, heart failure, and sleep apnoea. The once-monthly dosing is a meaningful convenience advantage, but the large molecule size requires cold-chain distribution. Whether GIP receptor blockade versus activation produces different long-term outcomes is a fundamental question that only head-to-head data against tirzepatide could answer.
PeptideTrace tracks 12 registered clinical trials for MariTide sourced from ClinicalTrials.gov.
Efficacy, Safety and Tolerability of Switching From Glucagon-like Peptide-1 Receptor Agonists (GLP-1RA) to Maridebart Cafraglutide in Adults With Obesity or Overweight (MARITIME-SWITCH)
Maridebart Cafraglutide Versus Placebo in Adult Participants With Obstructive Sleep Apnea on Positive Airway Pressure Therapy
A Trial to Compare the Extent to Which Maridebart Cafraglutide (AMG 133) is Made Available in the Body When Administered Using Two Subcutaneous Presentations
Maridebart Cafraglutide Versus Placebo in Adult Participants With Obstructive Sleep Apnea Not on Positive Airway Pressure (PAP) Therapy
Comparing the Extent to Which Maridebart Cafraglutide (AMG 133) is Made Available in the Body When Administered Using Two Subcutaneous (SC) Presentations
MariTide (maridebart cafraglutide; AMG 133) is a bispecific antibody-peptide conjugate developed by Amgen, consisting of a fully human anti-GIPR antagonist antibody conjugated at E384C positions to two GLP-1 agonist peptides. Molecular weight approximately 153,514 Da (153.5 kDa). NOTE: This is a large biologic, not a simple peptide. Half-life approximately 21 days, enabling once-monthly subcutaneous dosing. The Phase 3 MARITIME program has been initiated with optimized dosing regimens.
MariTide simultaneously activates GLP-1R (EC50 = 24.4 pM) while antagonizing GIPR (IC50 = 42.4 nM), representing the opposite GIP approach from tirzepatide which agonizes GIPR. Human genetic data support the rationale, as GIPR loss-of-function variants associate with lower BMI. The combined GLP-1 activation and GIP blockade produces weight loss exceeding GLP-1 agonism alone, with preliminary evidence suggesting favorable body composition effects including preferential fat mass reduction.
Phase 2 (Jastreboff et al., NEJM June 2025; NCT05669599; N=592): Cohort A (obesity without T2D; n=465) showed efficacy estimand weight loss of -16.3% to -19.9% across doses at 52 weeks versus -2.6% placebo; treatment policy -12.3% to -16.2%. DXA body composition substudy (n=191): fat mass reduction -26.2% to -36.8% with lean mass reduction only -8.6% to -11.6%. Cohort B (obesity plus T2D; n=127): efficacy estimand -12.1% to -17.0%; HbA1c -1.2 to -1.6 percentage points; 81-87% reached HbA1c at or below 6.5%. No weight loss plateau was observed at 52 weeks, and over 90% of participants entered the extension study.
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Semaglutide is one of the most extensively studied peptide medications available today, with clinical trial data spanning over 50,000 patients. It is sold as Ozempic for type 2 diabetes (approved 2017), Rybelsus as an oral tablet for diabetes (approved 2019), and Wegovy for weight management (approved 2021). Wegovy has since received additional approvals for reducing heart attack and stroke risk, for use in adolescents aged 12 and older, and for liver disease related to obesity. In clinical trials, patients taking Wegovy lost an average of 14.9% of their body weight over 68 weeks, and the SELECT trial demonstrated a 20% reduction in major cardiovascular events such as heart attack and stroke. Research is now exploring its potential in early Alzheimer's disease. The main side effects are gastrointestinal, particularly nausea, and a key limitation is that most weight tends to return after stopping treatment.
Bimagrumab is in Phase II/III development (not yet approved). A Phase II trial (75 patients with type 2 diabetes and obesity) showed 20.5% fat mass reduction with 3.6% lean mass increase — essentially reshaping body composition without net appetite suppression. The BELIEVE Phase IIb trial (507 patients) showed that bimagrumab plus semaglutide achieved 22% weight loss with the weight lost being 88% fat — significantly better body composition than semaglutide alone. Bimagrumab is not a peptide. Its strategic significance is as a combination partner to address the muscle loss problem inherent in weight loss with current obesity drugs. Eli Lilly's acquisition positions it alongside tirzepatide.
Pemvidutide is in Phase II/III development (not yet approved). In the MOMENTUM Phase II trial (391 patients, 48 weeks), the 2.4 mg dose achieved 15.6% weight loss. Body composition analysis showed 78% of weight lost was fat mass, with only 22% lean mass — a favourable ratio. A Phase IIb MASH trial (212 patients) showed MASH resolution in up to 75% of patients at the highest dose. Pemvidutide's balanced receptor profile and no-titration dosing regimen represent potential practical advantages. The high rate of MASH resolution in Phase II positions it as a candidate for liver disease indications alongside obesity.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
