Key facts
- MariTide (maridebart cafraglutide, formerly AMG 133) is Amgen’s antibody-peptide conjugate: a GIP receptor-blocking antibody joined to two GLP-1 analogue peptides.[2]
- In phase 2 it cut body weight by 12.3% to 16.2% at 52 weeks in people with obesity, against 2.5% on placebo (treatment-policy estimand).[1]
- It was given every 4 or every 8 weeks in phase 2, and its phase 1 half-life was a mean of 14 to 24 days.[1][2]
- The phase 3 MARITIME programme started in March 2025; the largest trial, MARITIME-CV, plans 12,800 participants.[8][10]
- MariTide is not approved anywhere. Amgen’s 3 Nov 2026 update lists only ongoing studies.[4][5]
What Is MariTide?
MariTide is the brand name Amgen uses for maridebart cafraglutide (AMG 133), an investigational obesity drug given by injection once every 4 weeks or less often, which produced up to 16.2% weight loss at 52 weeks in phase 2.[3][1]
| Feature | MariTide (maridebart cafraglutide) |
|---|---|
| Developer | Amgen[3] |
| Development code | AMG 133[2] |
| Molecule type | Antibody-peptide conjugate: a fully human anti-GIPR monoclonal antibody linked to two GLP-1 analogue peptides[2] |
| Mechanism | GLP-1 receptor agonist and GIP receptor antagonist[1] |
| Route and interval in phase 2 | Subcutaneous, every 4 weeks or every 8 weeks[1] |
| Half-life (phase 1) | Mean 14 to 24 days; peak levels 4 to 6 days after a dose[2] |
| Doses studied in phase 2 | 140, 280 and 420 mg[1] |
| Phase 2 weight loss, 52 weeks | -12.3% to -16.2% (obesity); -8.4% to -12.3% (obesity with type 2 diabetes)[1] |
| Phase 3 | MARITIME programme, ongoing[5] |
| Status | Investigational, not approved[4] |
Amgen says MariTide is the first long-acting antibody-peptide conjugate to combine GIP receptor antagonism with GLP-1 receptor agonism.[6] Tirzepatide takes the opposite approach to GIP: it is a once-weekly GIP and GLP-1 receptor agonist, so it activates the GIP receptor rather than blocking it.[16] For a wider view of the field, see GLP-1 alternatives.
How MariTide Works
MariTide works through two actions in one molecule: two GLP-1 analogue peptides activate the GLP-1 receptor, while the antibody backbone blocks the GIP receptor, and its mean half-life of 14 to 24 days allows dosing every 4 weeks or less often.[2]
- GLP-1 receptor agonism. The two GLP-1 analogue peptides are attached to the antibody with amino acid linkers, and cell tests confirmed GLP-1 receptor activation.[2]
- GIP receptor antagonism. The antibody is a fully human monoclonal antibody against the human GIP receptor, and cell tests confirmed it blocks that receptor.[2]
- Why block GIP. Amgen says human genetics work at its deCODE Genetics unit in Iceland pointed to blocking the GIP receptor, and preclinical studies found that activating GLP-1 while blocking GIP cut weight more than targeting either receptor alone.[6][3]
- Why monthly. The antibody gives the molecule a long half-life, about 21 days on average in phase 1, which the authors say enabled every-4-week dosing rather than the daily or weekly dosing of other GLP-1 drugs.[2]
- Less often still. Amgen now describes a design that starts with monthly dosing and may stay on as few as four or six doses a year, which phase 3 trials are testing.[5]
MariTide Phase 2 Results
In the 52-week phase 2 trial of 592 adults, MariTide cut body weight by 12.3% to 16.2% in people with obesity (placebo 2.5%) and by 8.4% to 12.3% in people with obesity and type 2 diabetes (placebo 1.7%), on the treatment-policy estimand.[1]
Highest MariTide arm in each cohort. Treatment-policy estimand from the NEJM paper; efficacy estimand (had everyone stayed on treatment) from Amgen.
| Cohort | Participants | Treatment policy | Efficacy estimand | Placebo |
|---|---|---|---|---|
| Obesity, no diabetes | 465 (63% female, mean BMI 37.9) | -12.3% to -16.2%[1] | -16.3% to -19.9%[4] | -2.5% (efficacy -2.6%)[1][4] |
| Obesity with type 2 diabetes | 127 (42% female, mean BMI 36.5) | -8.4% to -12.3%[1] | -12.1% to -17.0%[4] | -1.7% (efficacy -1.4%)[1][4] |
- In the type 2 diabetes cohort, HbA1c fell by 1.2 to 1.6 percentage points on MariTide against a 0.1-point rise on placebo (treatment policy); Amgen reports up to 2.2 points on the efficacy estimand.[1][4]
- Amgen says weight loss had not plateaued by week 52 in either cohort.[4]
- Amgen also reported improvements in waist circumference, blood pressure, hs-CRP and some lipids, and no link between MariTide and bone mineral density changes.[4][3]
- In phase 1, three doses of 420 mg every 4 weeks gave -14.5% by day 85, and weight was still 11.2% below baseline 150 days after the last dose.[2]
Part 2 of the trial re-randomised people who had lost at least 15% by week 52 to placebo, 70 mg, 140 mg or 420 mg monthly, or 420 mg every 12 weeks, to test maintenance and less frequent dosing.[4] Part 2 results were not in any primary source we could find.
MariTide Doses and Dosing Interval in Trials
Phase 2 tested 140, 280 and 420 mg every 4 weeks and 420 mg every 8 weeks, while phase 3 uses an 8-week escalation of 21 mg, then 35 mg, then 70 mg before one of three undisclosed target doses.[1][4]
| Trial | Doses studied | Interval and escalation | Length |
|---|---|---|---|
| Phase 1 SAD (n = 49) | 21 to 840 mg single dose | One dose, followed up to 150 days[2] | Up to 150 days |
| Phase 1 MAD (n = 26) | 140, 280 or 420 mg | Every 4 weeks, three doses, last on day 57[2] | Followed up to 150 days after the last dose |
| Phase 2, obesity (n = 465) | 140, 280 or 420 mg; 420 mg | Every 4 weeks without escalation; 420 mg every 8 weeks; or 420 mg every 4 weeks after a 4-week or 12-week escalation from 70 mg[1][4] | 52 weeks |
| Phase 2, obesity with type 2 diabetes (n = 127) | 140, 280 or 420 mg | Every 4 weeks, no escalation[1] | 52 weeks |
| Phase 1 PK-LDI (n = 121) | 21, 35 or 70 mg, then 70 mg, then 350 mg | Day 1, day 15 and day 29[4] | To day 43 |
| MARITIME-1 and MARITIME-2 | Low, medium or high dose | 21 mg, 35 mg, then 70 mg over 8 weeks, then target dose[4][8] | 72 weeks |
The MARITIME-1 and MARITIME-2 records on ClinicalTrials.gov list the arms only as low, medium and high dose, so the phase 3 target doses are not public.[8][9]
MariTide Side Effects
Nausea, vomiting and constipation were the most common MariTide side effects in phase 2, and in the dose escalation arms about 11% stopped treatment for any adverse event and up to 7.8% for gastrointestinal events.[3][4]
- Mostly early and mild. Amgen says nausea and vomiting were mostly mild, short-lived and linked mainly to the first dose; with escalation, nausea typically resolved within a median of 6 days and vomiting within 1 to 2 days.[3]
- Escalation helps. The NEJM paper reports that gastrointestinal events were common but less frequent with dose escalation and a lower starting dose, with no unexpected safety signals.[1]
- Lower starting doses. In the phase 1 PK-LDI study, overall vomiting was 24.4% with 21 mg/70 mg/350 mg and 22.5% with 35 mg/70 mg/350 mg, with no discontinuations for gastrointestinal events.[4]
- Phase 1. Nausea and vomiting mainly followed the first dose, started 8 to 12 hours after it and lasted about 72 hours; no severe or serious events or treatment-ending events were reported.[2]
Arm-by-arm nausea and vomiting rates for phase 2 are in the NEJM full text, which we could not open, and ClinicalTrials.gov had no posted results on 8 Nov 2026, so we do not give per-dose percentages here.[7] These dose escalation findings shaped the slower 21 mg start used in phase 3.[4]
MariTide Phase 3 (MARITIME Programme) and Approval Status as of Nov 2026
As of November 2026 MariTide is not approved; MARITIME-1 (3,853 people) and MARITIME-2 (1,105 people) are 72-week phase 3 weight trials with primary completion estimated for January 2027.[8][9]
| Trial | Population | Planned size | Status |
|---|---|---|---|
| MARITIME-1 (NCT06858839) | Obesity or overweight, no type 2 diabetes | 3,853 | Ongoing; started Mar 2025[8][5] |
| MARITIME-2 (NCT06858878) | Obesity or overweight with type 2 diabetes | 1,105 | Ongoing; started Mar 2025[9][5] |
| MARITIME-CV (NCT07037433) | Atherosclerotic cardiovascular disease with obesity or overweight | 12,800 | Enrolment complete[10][5] |
| MARITIME-HF (NCT07037459) | Heart failure (preserved or mildly reduced ejection fraction) with obesity | 5,056 | Enrolling[11][5] |
| MARITIME-SWITCH | Switching from weekly tirzepatide or semaglutide | Not stated | Enrolling; dosing every 8 weeks or quarterly[5] |
- Amgen also lists two sleep apnoea trials (enrolment complete), extension studies testing monthly, every-8-week and quarterly maintenance, and MARITIME-T2D-3 against semaglutide in type 2 diabetes.[5]
- Amgen plans two more phase 3 studies in type 2 diabetes in Q4 2026, and a phase 2b liver fat study has completed enrolment.[5]
- Amgen states that its product candidates are not approved by the US FDA, and its 3 Nov 2026 update describes no regulatory submission.[4][5]
MariTide vs Eloralintide
MariTide is an incretin drug given every 4 to 8 weeks with up to 16.2% weight loss at 52 weeks in phase 2, while Lilly’s eloralintide is a once-weekly amylin agonist with up to 20.1% at 48 weeks, on different estimands and with no head-to-head trial.[1][12]
| Feature | MariTide | Eloralintide |
|---|---|---|
| Developer | Amgen[3] | Eli Lilly[12] |
| Mechanism | GLP-1 receptor agonist and GIP receptor antagonist[1] | Selective amylin receptor agonist[12] |
| Molecule | Antibody-peptide conjugate[2] | Fatty-acid-acylated amylin analogue[14] |
| Interval in trials | Every 4 or 8 weeks[1] | Once weekly[13] |
| Half-life | Mean 14 to 24 days[2] | 310 to 366 hours (about 13 to 15 days)[14] |
| Best phase 2 weight loss | -16.2% at 52 wk (treatment policy); about -20% (efficacy)[1][4] | -20.1% at 48 wk, 9 mg (efficacy)[12] |
| Phase 3 | MARITIME, from Mar 2025[8] | ENLIGHTEN, from Feb 2026[15] |
The two drugs act on different hormone systems, so they are studied as different kinds of treatment rather than rivals in the same class. More on each: what is eloralintide, eloralintide vs tirzepatide and GLP-1 alternatives.
Frequently Asked Questions
What is MariTide?
MariTide is Amgen’s name for maridebart cafraglutide (AMG 133), an investigational obesity drug. It is an antibody joined to two GLP-1 peptides: it activates the GLP-1 receptor and blocks the GIP receptor, and is injected every 4 weeks or less often in trials.
How much weight do people lose on MariTide?
In the 52-week phase 2 trial, people with obesity lost 12.3% to 16.2% of body weight on MariTide against 2.5% on placebo. People with obesity and type 2 diabetes lost 8.4% to 12.3% against 1.7%. Amgen reports up to about 20% had everyone stayed on treatment.
How often is MariTide injected?
Every 4 weeks in most phase 2 arms, with one arm every 8 weeks. Phase 3 extension and switch trials are testing every-8-week and quarterly dosing for maintenance. This is trial data, not advice.
What are the side effects of MariTide?
Mainly nausea, vomiting and constipation, mostly mild and concentrated around the first dose. Starting lower and escalating reduced them, and in the escalation arms up to 7.8% stopped treatment for gastrointestinal events.
Is MariTide FDA approved?
No. MariTide is investigational and not approved by the FDA or any other regulator. Amgen’s November 2026 update lists it only in ongoing phase 3 MARITIME trials.
What is the difference between MariTide and Zepbound?
Both target the GLP-1 receptor, but tirzepatide (Zepbound) also activates the GIP receptor while MariTide blocks it. Tirzepatide is a weekly peptide; MariTide is an antibody-peptide conjugate given monthly or less often in trials.
Sources
- Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity: a phase 2 trial. N Engl J Med 2025;393(9):843-857. DOI 10.1056/NEJMoa2504214
- 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. Nature Metabolism 2024;6(2):290-303. DOI 10.1038/s42255-023-00966-w
- Amgen press release, 26 Nov 2024: MariTide 52-week phase 2 topline results
- Amgen press release, 23 Jun 2025: MariTide phase 2 full results and phase 1 PK-LDI data at ADA 2025
- Amgen third quarter 2026 financial results, 3 Nov 2026 (MariTide pipeline update)
- Amgen story, 11 May 2026: The story of maridebart cafraglutide (MariTide)
- ClinicalTrials.gov NCT05669599, MariTide (AMG 133) phase 2 dose-ranging study
- ClinicalTrials.gov NCT06858839, MARITIME-1
- ClinicalTrials.gov NCT06858878, MARITIME-2
- ClinicalTrials.gov NCT07037433, MARITIME-CV
- ClinicalTrials.gov NCT07037459, MARITIME-HF
- Eli Lilly press release, 6 Nov 2025: eloralintide phase 2 results
- Billings LK, et al. Eloralintide phase 2, 48-week trial. The Lancet 2025;406:2631-2643. DOI 10.1016/S0140-6736(25)02155-5
- Briere DA, et al. Discovery and first-in-human study of eloralintide. Molecular Metabolism 2025;102:102271. DOI 10.1016/j.molmet.2025.102271
- ClinicalTrials.gov NCT07321886, ENLIGHTEN-1
- Jastreboff AM, et al. Tirzepatide SURMOUNT-1. N Engl J Med 2022;387:205-216. DOI 10.1056/NEJMoa2206038
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