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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Danuglipron's original twice-daily formulation achieved 8–13% weight loss in Phase IIb but with treatment discontinuation rates exceeding 50%, with nausea affecting up to 73% of patients. Pfizer discontinued the twice-daily formulation and is developing a once-daily modified-release version. Danuglipron is not a peptide. Its development trajectory illustrates that even effective weight loss compounds can fail commercially if tolerability is inadequate. The reformulation effort aims to reduce peak drug concentrations that likely drive the gastrointestinal side effects.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
CT-388 is in Phase II/III development (not yet approved). Phase II results (469 patients, 48 weeks) showed 22.5% placebo-adjusted weight loss at the highest dose, with low discontinuation rates due to adverse events (5.9%). Phase III trials are underway. The combination of high efficacy and low discontinuation rates in Phase II is notable — many obesity drugs achieve high weight loss but suffer from tolerability-driven dropouts. Roche's $2.7 billion acquisition of the developer signals significant confidence in the programme.
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.
