Maridebart cafraglutide

updated

Maridebart cafraglutide (MariTide) is Amgen's investigational antibody-peptide conjugate: a GIP receptor antagonist antibody joined to two GLP-1 receptor agonist peptides, given by subcutaneous injection. In a 592-person phase 2 trial published in the New England Journal of Medicine, mean percent change in body weight at 52 weeks in the obesity cohort ranged from -12.3% to -16.2% across regimens versus -2.5% on placebo (treatment policy estimand, change from baseline). The two phase 3 weight-management trials are fully enrolled and have no results, and no US approval exists.

GIP receptor antagonist antibody conjugated to GLP-1 receptor agonist peptides

  • Maridebart cafraglutide is a WHO Proposed INN (List 128, 2022) for a fully human anti-human GIPR IgG1-kappa monoclonal antibody conjugated to two identical GLP-1 analogue peptides. Its stated action is GIP receptor antagonist and GLP-1 receptor agonist. Amgen is the developer, and MariTide and AMG 133 are other names.
  • In the phase 2 trial (NCT05669599, 465 adults with obesity), mean percent change in body weight to week 52 ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) across regimens versus -2.5% (95% CI -4.2 to -0.7) on placebo, by the treatment policy estimand. These are changes from baseline, not placebo-adjusted differences.
  • Amgen's 23 June 2025 press release reported 16.3% to 19.9% weight change by the efficacy estimand versus 2.6% on placebo in the obesity cohort. That estimand models full adherence for 52 weeks, so it gives larger figures than the treatment policy analysis in the paper.
  • In the phase 1 study (75 participants), the mean terminal half-life ranged from 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6.
  • MARITIME-1 (NCT06858839, 3,853 enrolled) and MARITIME-2 (NCT06858878, 1,105 enrolled) are Active, not recruiting, with a week 72 weight endpoint and estimated primary completion on 21 January 2027. Neither has posted results.
  • On 10 October 2026, openFDA Drugs@FDA returned no application records for maridebart cafraglutide and a DailyMed search returned no labels.

What is maridebart cafraglutide, and is it approved?

Maridebart cafraglutide (MariTide) is Amgen's antibody-peptide conjugate: a GIP receptor antagonist antibody joined to two GLP-1 receptor agonist peptides. No US approval exists: openFDA and DailyMed searches on 10 October 2026 returned no application records and no labels.

Maridebart cafraglutide is a WHO Proposed INN (List 128, WHO Drug Information Vol. 36 No. 4, 2022), defined as a fully human anti-human GIPR IgG1-kappa monoclonal antibody conjugated to two identical GLP-1 analogue peptides, with the stated action GIP receptor antagonist and GLP-1 receptor agonist. List 133 (Vol. 39 No. 2, 2025) republishes the entry with a replaced chemical name. It is an antibody-peptide conjugate, not a single peptide. A PubChem name search for maridebart cafraglutide and MariTide returned no compound record on 10 October 2026, so no formula, molecular weight or sequence is given here.

Amgen is the developer. ClinicalTrials.gov lists Amgen as sponsor of MARITIME-1 (NCT06858839) with the intervention maridebart cafraglutide and the other names AMG 133 and MariTide. Amgen's 23 June 2025 press release calls it MariTide (maridebart cafraglutide, formerly AMG 133), and its 4 August 2026 earnings release heads the section MariTide (maridebart cafraglutide/AMG 133).

On 10 October 2026 openFDA Drugs@FDA returned no application records for maridebart cafraglutide, and a DailyMed search returned no labels. Only US regulator databases were searched. The pivotal phase 3 trials are ongoing and none has posted results.

WHO Proposed INN List 128 (2022): antibody-peptide conjugate, GIP antagonist and GLP-1 agonist

Chemical identity record

World Health Organization. Proposed International Nonproprietary Names: List 128. WHO Drug Information, Vol. 36, No. 4, 2022. List 133 (Vol. 39, No. 2, 2025) republishes the entry with a replaced chemical name.

Maridebart cafraglutide is defined as a fully human anti-human GIPR IgG1-kappa monoclonal antibody conjugated to two identical GLP-1 analogue peptides, with the stated action GIP receptor antagonist and GLP-1 receptor agonist. It is an antibody-peptide conjugate, not a single peptide, and it antagonizes the GIP receptor. A PubChem name search for maridebart cafraglutide and MariTide returned no compound record on 10 October 2026.

Participants / model
Molecular identity, not a clinical population
Treatment
Antibody-peptide conjugate, subcutaneous
Follow-up
Not applicable
Study design
Official WHO nomenclature record (Proposed INN list)
Funding
not stated in the source

Because the GIP receptor is antagonized, the compound is not a GLP-1 and GIP receptor co-agonist of the kind tirzepatide is.

Read the original source
Registry: MARITIME-1 and MARITIME-2, Amgen sponsor, Active not recruiting, no posted results

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Record NCT06858839 (MARITIME-1), with record NCT06858878 (MARITIME-2). Read on 10 October 2026.

ClinicalTrials.gov lists Amgen as sponsor of MARITIME-1 with the intervention maridebart cafraglutide and the other names AMG 133 and MariTide. MARITIME-1: adults without type 2 diabetes, 3,853 participants enrolled, primary endpoint percent change in body weight at week 72, status Active, not recruiting, start 12 March 2025, estimated primary completion 21 January 2027. MARITIME-2 (NCT06858878): adults with type 2 diabetes, 1,105 enrolled, same endpoint and primary completion date, status Active, not recruiting. Neither record has posted results. A registration without posted results is not an outcome.

Participants / model
Adults with obesity or overweight, without and with type 2 diabetes (planned)
Treatment
Subcutaneous maridebart cafraglutide versus placebo, 72 weeks
Follow-up
72 weeks per participant; estimated primary completion 21 January 2027
Study design
Registered phase 3 design and status only
Funding
Sponsor: Amgen

Registry design and status only. No efficacy or safety result from either trial is public.

Read the original source
Company statement, 23 June 2025: efficacy estimand 16.3% to 19.9%, GI discontinuations up to 7.8%

Regulatory record

Amgen press release dated 23 June 2025, reporting results of the phase 2 MariTide obesity study presented at the American Diabetes Association 85th Scientific Sessions.

By the efficacy estimand, weight change at week 52 ranged from 16.3% to 19.9% with MariTide versus 2.6% on placebo in the obesity cohort, and from 12.1% to 17.0% versus 1.4% in the type 2 diabetes cohort. Amgen reports discontinuation due to gastrointestinal adverse events in the dose-escalation arms of up to 7.8%, lower than in the arms without escalation, and says no new safety signals were identified. The treatment policy numbers in the release match the New England Journal of Medicine paper. Amgen's footnote defines the efficacy estimand as the effect had participants adhered for the full 52 weeks (missing data after early discontinuation are estimated from individual response) and the treatment policy estimand as the intent-to-treat analysis, so the efficacy figures are the larger ones.

Participants / model
Adults with obesity, with and without type 2 diabetes
Treatment
Subcutaneous MariTide, 52 weeks
Follow-up
52 weeks
Study design
Company press release on the phase 2 trial; not peer reviewed
Funding
not stated in the source

The efficacy estimand figures are larger than the treatment policy figures in the paper because the efficacy estimand models full adherence. They are company-reported and are not placebo-adjusted.

Read the original source
Company filing, 4 August 2026: MARITIME program ongoing, further phase 3 studies enrolling

Regulatory record

Amgen Inc. earnings release for the second quarter of 2026, filed 4 August 2026 as an exhibit with the U.S. Securities and Exchange Commission.

MARITIME-1 and MARITIME-2 are ongoing, and Amgen lists further phase 3 studies as enrolling: MARITIME-CV (cardiovascular outcomes, NCT07037433, estimated 12,800 participants), MARITIME-HF, MARITIME-OSA-1, MARITIME-OSA-2, MARITIME-SWITCH (from weekly tirzepatide or semaglutide to MariTide every 8 weeks or quarterly), and long-term extensions of MARITIME-1 and MARITIME-2. Amgen also says three phase 3 studies in type 2 diabetes will start in 2026. The release heads the section MariTide (maridebart cafraglutide/AMG 133).

Participants / model
Adults with obesity or overweight and related conditions (planned)
Treatment
Subcutaneous MariTide, monthly, every 8 weeks, or quarterly
Follow-up
Program status as of 4 August 2026
Study design
Company filing (earnings release, SEC exhibit); program status only
Funding
not stated in the source

Program status only. No phase 3 efficacy, safety or outcome data are reported.

Read the original source
Searches, 10 October 2026: no US application or label, no phase 3 result

PubMed search record

PubMed search for maridebart cafraglutide, run on 10 October 2026 (14 records). ClinicalTrials.gov search for maridebart OR MariTide OR AMG-133 run the same day (29 records). openFDA Drugs@FDA and DailyMed searches run the same day.

No US approval exists: on 10 October 2026 openFDA Drugs@FDA returned no application records for maridebart cafraglutide and a DailyMed search returned no labels. A PubMed search the same day returned 14 records: the phase 2 trial paper, three correspondence items on it, the phase 1 paper, one mouse study, seven reviews and one unrelated bariatric surgery audit. None reports a phase 3 result. A ClinicalTrials.gov search for maridebart OR MariTide OR AMG-133 returned 29 records (15 phase 1, 3 phase 2, 11 phase 3); the only posted results are for two phase 1 studies (NCT04478708 and NCT05056246), and no MARITIME trial has posted results.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Literature, registry and regulator searches
Funding
not stated in the source

A search result shows what the databases returned on that date. Only US regulator databases were searched. It is not proof that no unindexed study exists.

Read the original source

What did the phase 2 trial find?

In the 592-person phase 2 trial published in the New England Journal of Medicine, mean percent change in body weight to week 52 in the obesity cohort ranged from -12.3% to -16.2% across regimens versus -2.5% on placebo (treatment policy estimand). The type 2 diabetes cohort ranged from -8.4% to -12.3% versus -1.7%.

The phase 2 trial (NCT05669599, funded by Amgen) was double-blind, randomized, placebo-controlled and dose-ranging, and enrolled 592 participants in two cohorts. Maridebart cafraglutide was given by subcutaneous injection every 4 or 8 weeks for 52 weeks. The regimens were 140, 280 or 420 mg every 4 weeks without dose escalation, 420 mg every 8 weeks, and 420 mg every 4 weeks with a 4-week or 12-week dose escalation.

The obesity cohort had 465 participants (63% female, mean age 47.9, mean BMI 37.9). Mean percent change in body weight to week 52, by the treatment policy estimand, ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) across maridebart cafraglutide regimens versus -2.5% (95% CI -4.2 to -0.7) on placebo. These are changes from baseline in each arm, not placebo-adjusted differences.

The obesity-with-type 2 diabetes cohort had 127 participants. Mean percent change in body weight ranged from -8.4% (95% CI -11.0 to -5.7) to -12.3% (95% CI -15.3 to -9.2) versus -1.7% (95% CI -2.9 to -0.6) on placebo, with HbA1c changing by -1.2 to -1.6 percentage points versus +0.1 on placebo.

Phase 2: 592 adults, 52 weeks, -12.3% to -16.2% versus -2.5% (obesity cohort, treatment policy estimand)

Randomized controlled trial

Jastreboff AM et al. N Engl J Med. 2025;393(9):843-857. PMID 40549887.

Obesity cohort (465 participants, 63% female, mean age 47.9, mean BMI 37.9): mean percent change in body weight to week 52, treatment policy estimand, ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) across maridebart cafraglutide regimens versus -2.5% (95% CI -4.2 to -0.7) on placebo. Obesity-with-type 2 diabetes cohort (127 participants): -8.4% (95% CI -11.0 to -5.7) to -12.3% (95% CI -15.3 to -9.2) versus -1.7% (95% CI -2.9 to -0.6), with HbA1c change of -1.2 to -1.6 percentage points versus +0.1 on placebo. The authors report gastrointestinal adverse events were common, less frequent with dose escalation and a lower starting dose, and that no unexpected safety signals emerged.

Participants / model
592 adults with obesity, with and without type 2 diabetes, in two cohorts
Treatment
Subcutaneous maridebart cafraglutide every 4 or 8 weeks: 140, 280 or 420 mg every 4 weeks without dose escalation, 420 mg every 8 weeks, and 420 mg every 4 weeks with 4-week or 12-week dose escalation
Follow-up
52 weeks
Study design
Double-blind, randomized, placebo-controlled, dose-ranging phase 2 trial (NCT05669599)
Funding
Funded by Amgen

The weight figures are mean percent change in body weight by the treatment policy estimand, each arm against its own placebo value, not placebo-adjusted differences. The full text was not retrieved, so only abstract-level safety is given.

Read the original source

What did the phase 1 study show about weight and half-life?

In the phase 1 study (75 participants with obesity), mean terminal half-life ranged from 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6. In the 420 mg every-4-weeks group, mean body weight change was -14.5% by day 85.

The phase 1 study (NCT04478708) was a randomized, double-blind, placebo-controlled single- and multiple-ascending-dose study in participants with obesity at three US sites. It gave subcutaneous AMG 133 as single doses of 21 to 840 mg and as every-4-weeks multiple doses. The paper reports the final analysis of 75 participants in five single-dose and three multiple-dose cohorts.

In the 420 mg every-4-weeks multiple-dose group, mean body weight change was -14.5% by day 85 and was still -11.2% 150 days after the last dose. The sources reviewed do not say whether these figures are placebo-adjusted. The mean terminal half-life in people ranged from 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6.

Phase 1: 75 participants, half-life about 21 days, -14.5% at day 85 in the 420 mg group

Clinical trial

Véniant MM et al. Nat Metab. 2024;6(2):290-303. PMID 38316982.

The paper reports the final analysis of 75 participants in five single-dose and three multiple-dose cohorts. In the 420 mg every-4-weeks multiple-dose group, mean body weight change was -14.5% by day 85 and was still -11.2% 150 days after the last dose. The human mean terminal half-life ranged from 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6. The most common adverse events were nausea and vomiting, mostly mild and resolving within 48 hours, and no severe or serious adverse events or adverse events leading to permanent discontinuation were reported.

Participants / model
Adults with obesity (75 participants in the reported cohorts) at three US sites
Treatment
Subcutaneous AMG 133, single doses of 21 to 840 mg and every-4-weeks multiple doses
Follow-up
Single doses; multiple doses every 4 weeks; follow-up to 150 days after the last dose
Study design
Randomized, double-blind, placebo-controlled single- and multiple-ascending-dose phase 1 trial with preclinical data (NCT04478708)
Funding
not stated in the source

The sources reviewed do not say whether the weight figures are placebo-adjusted.

Read the original source

What has Amgen reported that no paper shows?

Amgen's 23 June 2025 press release gave efficacy estimand results for the phase 2 trial: 16.3% to 19.9% weight change versus 2.6% on placebo in the obesity cohort. Later earnings releases describe a completed extension and a type 2 diabetes phase 2 result with no numbers. These are company statements, and the extension and diabetes results have no paper.

On 23 June 2025 Amgen reported the same phase 2 trial in a press release. By the efficacy estimand, weight change at week 52 ranged from 16.3% to 19.9% with MariTide versus 2.6% on placebo in the obesity cohort, and from 12.1% to 17.0% versus 1.4% in the type 2 diabetes cohort. These are each arm's change from baseline, not placebo-adjusted differences. Amgen's footnote defines the efficacy estimand as the effect had participants adhered for the full 52 weeks, with missing data after early discontinuation estimated from individual response, and the treatment policy estimand as the intent-to-treat analysis, so the efficacy figures are the larger ones. The treatment policy numbers in the release match the New England Journal of Medicine paper.

Amgen's fourth-quarter 2025 earnings release of 3 February 2026 gave no numbers for two further results. Part 2 of the phase 2 study, an exploratory 52-week extension in people who lost at least 15% of body weight in Part 1, is complete. The company said the large majority kept their weight loss for an additional 52 weeks on a lower monthly dose or a quarterly dose, with a very low incidence of nausea and vomiting and no new safety signals. A separate phase 2 study in type 2 diabetes (NCT06660173) reached its 24-week point with reductions in HbA1c and weight and a safety profile Amgen calls consistent with the GLP-1 class. Neither result has a published paper or a number in the records reviewed.

Company statement, 23 June 2025: efficacy estimand 16.3% to 19.9%, GI discontinuations up to 7.8%

Regulatory record

Amgen press release dated 23 June 2025, reporting results of the phase 2 MariTide obesity study presented at the American Diabetes Association 85th Scientific Sessions.

By the efficacy estimand, weight change at week 52 ranged from 16.3% to 19.9% with MariTide versus 2.6% on placebo in the obesity cohort, and from 12.1% to 17.0% versus 1.4% in the type 2 diabetes cohort. Amgen reports discontinuation due to gastrointestinal adverse events in the dose-escalation arms of up to 7.8%, lower than in the arms without escalation, and says no new safety signals were identified. The treatment policy numbers in the release match the New England Journal of Medicine paper. Amgen's footnote defines the efficacy estimand as the effect had participants adhered for the full 52 weeks (missing data after early discontinuation are estimated from individual response) and the treatment policy estimand as the intent-to-treat analysis, so the efficacy figures are the larger ones.

Participants / model
Adults with obesity, with and without type 2 diabetes
Treatment
Subcutaneous MariTide, 52 weeks
Follow-up
52 weeks
Study design
Company press release on the phase 2 trial; not peer reviewed
Funding
not stated in the source

The efficacy estimand figures are larger than the treatment policy figures in the paper because the efficacy estimand models full adherence. They are company-reported and are not placebo-adjusted.

Read the original source
Company statement, 3 February 2026: Part 2 extension and type 2 diabetes phase 2, no numbers

Regulatory record

Amgen Inc. earnings release for the fourth quarter of 2025, dated 3 February 2026, filed as an exhibit with the U.S. Securities and Exchange Commission.

Part 2 of the phase 2 study, an exploratory 52-week extension in people who lost at least 15% of body weight in Part 1, is complete: the large majority kept their weight loss for an additional 52 weeks on a lower monthly dose or a quarterly dose, with a very low incidence of nausea and vomiting and no new safety signals. A separate phase 2 study in type 2 diabetes (NCT06660173) reached its 24-week point with reductions in HbA1c and weight and a safety profile Amgen calls consistent with the GLP-1 class. Neither result has a published paper or a number in the records reviewed.

Participants / model
Adults who lost at least 15% in Part 1; adults with type 2 diabetes
Treatment
Subcutaneous MariTide, lower monthly or quarterly doses
Follow-up
52-week extension; 24 weeks in the type 2 diabetes study
Study design
Company earnings release; not peer reviewed, and no numbers given
Funding
not stated in the source

Company statement without numbers. No paper for either result was found in the records reviewed.

Read the original source
Phase 2: 592 adults, 52 weeks, -12.3% to -16.2% versus -2.5% (obesity cohort, treatment policy estimand)

Randomized controlled trial

Jastreboff AM et al. N Engl J Med. 2025;393(9):843-857. PMID 40549887.

Obesity cohort (465 participants, 63% female, mean age 47.9, mean BMI 37.9): mean percent change in body weight to week 52, treatment policy estimand, ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) across maridebart cafraglutide regimens versus -2.5% (95% CI -4.2 to -0.7) on placebo. Obesity-with-type 2 diabetes cohort (127 participants): -8.4% (95% CI -11.0 to -5.7) to -12.3% (95% CI -15.3 to -9.2) versus -1.7% (95% CI -2.9 to -0.6), with HbA1c change of -1.2 to -1.6 percentage points versus +0.1 on placebo. The authors report gastrointestinal adverse events were common, less frequent with dose escalation and a lower starting dose, and that no unexpected safety signals emerged.

Participants / model
592 adults with obesity, with and without type 2 diabetes, in two cohorts
Treatment
Subcutaneous maridebart cafraglutide every 4 or 8 weeks: 140, 280 or 420 mg every 4 weeks without dose escalation, 420 mg every 8 weeks, and 420 mg every 4 weeks with 4-week or 12-week dose escalation
Follow-up
52 weeks
Study design
Double-blind, randomized, placebo-controlled, dose-ranging phase 2 trial (NCT05669599)
Funding
Funded by Amgen

The weight figures are mean percent change in body weight by the treatment policy estimand, each arm against its own placebo value, not placebo-adjusted differences. The full text was not retrieved, so only abstract-level safety is given.

Read the original source

What is in the phase 3 program, and does it have results?

None of the phase 3 trials has posted results. MARITIME-1 (3,853 adults without type 2 diabetes) and MARITIME-2 (1,105 adults with type 2 diabetes) are fully enrolled with a week 72 weight endpoint, and Amgen lists further phase 3 studies, including a cardiovascular outcomes trial, as enrolling.

MARITIME-1 (NCT06858839) enrolled 3,853 adults without type 2 diabetes. Its primary endpoint is percent change in body weight at week 72, its status is Active, not recruiting, it started on 12 March 2025, and its estimated primary completion is 21 January 2027. MARITIME-2 (NCT06858878) enrolled 1,105 adults with type 2 diabetes, with the same endpoint, the same estimated primary completion date and the same status. Neither record has posted results.

Amgen's second-quarter 2026 earnings release, filed on 4 August 2026, says MARITIME-1 and MARITIME-2 are ongoing and lists further phase 3 studies as enrolling: MARITIME-CV (cardiovascular outcomes, NCT07037433, estimated 12,800 participants), MARITIME-HF, MARITIME-OSA-1, MARITIME-OSA-2, MARITIME-SWITCH (from weekly tirzepatide or semaglutide to MariTide every 8 weeks or quarterly), and long-term extensions of MARITIME-1 and MARITIME-2. Amgen also says three phase 3 studies in type 2 diabetes will start in 2026.

A registration without posted results is not an outcome. A ClinicalTrials.gov search for maridebart OR MariTide OR AMG-133 on 10 October 2026 returned 29 records (15 phase 1, 3 phase 2, 11 phase 3). The only posted results are for two phase 1 studies (NCT04478708 and NCT05056246), and no MARITIME trial has posted results. A PubMed search for maridebart cafraglutide the same day returned 14 records, and none reports a phase 3 result.

Registry: MARITIME-1 and MARITIME-2, Amgen sponsor, Active not recruiting, no posted results

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Record NCT06858839 (MARITIME-1), with record NCT06858878 (MARITIME-2). Read on 10 October 2026.

ClinicalTrials.gov lists Amgen as sponsor of MARITIME-1 with the intervention maridebart cafraglutide and the other names AMG 133 and MariTide. MARITIME-1: adults without type 2 diabetes, 3,853 participants enrolled, primary endpoint percent change in body weight at week 72, status Active, not recruiting, start 12 March 2025, estimated primary completion 21 January 2027. MARITIME-2 (NCT06858878): adults with type 2 diabetes, 1,105 enrolled, same endpoint and primary completion date, status Active, not recruiting. Neither record has posted results. A registration without posted results is not an outcome.

Participants / model
Adults with obesity or overweight, without and with type 2 diabetes (planned)
Treatment
Subcutaneous maridebart cafraglutide versus placebo, 72 weeks
Follow-up
72 weeks per participant; estimated primary completion 21 January 2027
Study design
Registered phase 3 design and status only
Funding
Sponsor: Amgen

Registry design and status only. No efficacy or safety result from either trial is public.

Read the original source
Company filing, 4 August 2026: MARITIME program ongoing, further phase 3 studies enrolling

Regulatory record

Amgen Inc. earnings release for the second quarter of 2026, filed 4 August 2026 as an exhibit with the U.S. Securities and Exchange Commission.

MARITIME-1 and MARITIME-2 are ongoing, and Amgen lists further phase 3 studies as enrolling: MARITIME-CV (cardiovascular outcomes, NCT07037433, estimated 12,800 participants), MARITIME-HF, MARITIME-OSA-1, MARITIME-OSA-2, MARITIME-SWITCH (from weekly tirzepatide or semaglutide to MariTide every 8 weeks or quarterly), and long-term extensions of MARITIME-1 and MARITIME-2. Amgen also says three phase 3 studies in type 2 diabetes will start in 2026. The release heads the section MariTide (maridebart cafraglutide/AMG 133).

Participants / model
Adults with obesity or overweight and related conditions (planned)
Treatment
Subcutaneous MariTide, monthly, every 8 weeks, or quarterly
Follow-up
Program status as of 4 August 2026
Study design
Company filing (earnings release, SEC exhibit); program status only
Funding
not stated in the source

Program status only. No phase 3 efficacy, safety or outcome data are reported.

Read the original source
Searches, 10 October 2026: no US application or label, no phase 3 result

PubMed search record

PubMed search for maridebart cafraglutide, run on 10 October 2026 (14 records). ClinicalTrials.gov search for maridebart OR MariTide OR AMG-133 run the same day (29 records). openFDA Drugs@FDA and DailyMed searches run the same day.

No US approval exists: on 10 October 2026 openFDA Drugs@FDA returned no application records for maridebart cafraglutide and a DailyMed search returned no labels. A PubMed search the same day returned 14 records: the phase 2 trial paper, three correspondence items on it, the phase 1 paper, one mouse study, seven reviews and one unrelated bariatric surgery audit. None reports a phase 3 result. A ClinicalTrials.gov search for maridebart OR MariTide OR AMG-133 returned 29 records (15 phase 1, 3 phase 2, 11 phase 3); the only posted results are for two phase 1 studies (NCT04478708 and NCT05056246), and no MARITIME trial has posted results.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Literature, registry and regulator searches
Funding
not stated in the source

A search result shows what the databases returned on that date. Only US regulator databases were searched. It is not proof that no unindexed study exists.

Read the original source

Is MariTide a GLP-1 agonist plus GIP antagonist antibody, dosed monthly, and in phase 3?

Yes on all three points, with one correction: the GIP receptor is blocked, not activated, so MariTide does not activate both receptors the way tirzepatide does. Dosing every 4 weeks was used in the phase 1 and phase 2 studies, and phase 3 is under way with no results.

The claim is that maridebart cafraglutide (MariTide, Amgen) is a GLP-1 agonist plus GIP antagonist antibody conjugate, dosed monthly, and in phase 3. The naming record supports the first part: the proposed INN describes a GIP receptor antagonist antibody conjugated to two GLP-1 analogue peptides, with the stated action GIP receptor antagonist and GLP-1 receptor agonist. The correction is that the compound antagonizes the GIP receptor, so it should not be described as acting like tirzepatide, which activates both receptors.

Dosing every 4 weeks, which is the monthly regimen in the claim, was used in the phase 1 multiple-dose cohorts and in phase 2 regimens. Phase 2 also tested 420 mg every 8 weeks, and Amgen's later releases describe every-8-week and quarterly regimens, which rest on company statements. Phase 3 is registered and under way: MARITIME-1 and MARITIME-2 are Active, not recruiting, with no results.

WHO Proposed INN List 128 (2022): antibody-peptide conjugate, GIP antagonist and GLP-1 agonist

Chemical identity record

World Health Organization. Proposed International Nonproprietary Names: List 128. WHO Drug Information, Vol. 36, No. 4, 2022. List 133 (Vol. 39, No. 2, 2025) republishes the entry with a replaced chemical name.

Maridebart cafraglutide is defined as a fully human anti-human GIPR IgG1-kappa monoclonal antibody conjugated to two identical GLP-1 analogue peptides, with the stated action GIP receptor antagonist and GLP-1 receptor agonist. It is an antibody-peptide conjugate, not a single peptide, and it antagonizes the GIP receptor. A PubChem name search for maridebart cafraglutide and MariTide returned no compound record on 10 October 2026.

Participants / model
Molecular identity, not a clinical population
Treatment
Antibody-peptide conjugate, subcutaneous
Follow-up
Not applicable
Study design
Official WHO nomenclature record (Proposed INN list)
Funding
not stated in the source

Because the GIP receptor is antagonized, the compound is not a GLP-1 and GIP receptor co-agonist of the kind tirzepatide is.

Read the original source
Phase 1: 75 participants, half-life about 21 days, -14.5% at day 85 in the 420 mg group

Clinical trial

Véniant MM et al. Nat Metab. 2024;6(2):290-303. PMID 38316982.

The paper reports the final analysis of 75 participants in five single-dose and three multiple-dose cohorts. In the 420 mg every-4-weeks multiple-dose group, mean body weight change was -14.5% by day 85 and was still -11.2% 150 days after the last dose. The human mean terminal half-life ranged from 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6. The most common adverse events were nausea and vomiting, mostly mild and resolving within 48 hours, and no severe or serious adverse events or adverse events leading to permanent discontinuation were reported.

Participants / model
Adults with obesity (75 participants in the reported cohorts) at three US sites
Treatment
Subcutaneous AMG 133, single doses of 21 to 840 mg and every-4-weeks multiple doses
Follow-up
Single doses; multiple doses every 4 weeks; follow-up to 150 days after the last dose
Study design
Randomized, double-blind, placebo-controlled single- and multiple-ascending-dose phase 1 trial with preclinical data (NCT04478708)
Funding
not stated in the source

The sources reviewed do not say whether the weight figures are placebo-adjusted.

Read the original source
Phase 2: 592 adults, 52 weeks, -12.3% to -16.2% versus -2.5% (obesity cohort, treatment policy estimand)

Randomized controlled trial

Jastreboff AM et al. N Engl J Med. 2025;393(9):843-857. PMID 40549887.

Obesity cohort (465 participants, 63% female, mean age 47.9, mean BMI 37.9): mean percent change in body weight to week 52, treatment policy estimand, ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) across maridebart cafraglutide regimens versus -2.5% (95% CI -4.2 to -0.7) on placebo. Obesity-with-type 2 diabetes cohort (127 participants): -8.4% (95% CI -11.0 to -5.7) to -12.3% (95% CI -15.3 to -9.2) versus -1.7% (95% CI -2.9 to -0.6), with HbA1c change of -1.2 to -1.6 percentage points versus +0.1 on placebo. The authors report gastrointestinal adverse events were common, less frequent with dose escalation and a lower starting dose, and that no unexpected safety signals emerged.

Participants / model
592 adults with obesity, with and without type 2 diabetes, in two cohorts
Treatment
Subcutaneous maridebart cafraglutide every 4 or 8 weeks: 140, 280 or 420 mg every 4 weeks without dose escalation, 420 mg every 8 weeks, and 420 mg every 4 weeks with 4-week or 12-week dose escalation
Follow-up
52 weeks
Study design
Double-blind, randomized, placebo-controlled, dose-ranging phase 2 trial (NCT05669599)
Funding
Funded by Amgen

The weight figures are mean percent change in body weight by the treatment policy estimand, each arm against its own placebo value, not placebo-adjusted differences. The full text was not retrieved, so only abstract-level safety is given.

Read the original source
Registry: MARITIME-1 and MARITIME-2, Amgen sponsor, Active not recruiting, no posted results

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Record NCT06858839 (MARITIME-1), with record NCT06858878 (MARITIME-2). Read on 10 October 2026.

ClinicalTrials.gov lists Amgen as sponsor of MARITIME-1 with the intervention maridebart cafraglutide and the other names AMG 133 and MariTide. MARITIME-1: adults without type 2 diabetes, 3,853 participants enrolled, primary endpoint percent change in body weight at week 72, status Active, not recruiting, start 12 March 2025, estimated primary completion 21 January 2027. MARITIME-2 (NCT06858878): adults with type 2 diabetes, 1,105 enrolled, same endpoint and primary completion date, status Active, not recruiting. Neither record has posted results. A registration without posted results is not an outcome.

Participants / model
Adults with obesity or overweight, without and with type 2 diabetes (planned)
Treatment
Subcutaneous maridebart cafraglutide versus placebo, 72 weeks
Follow-up
72 weeks per participant; estimated primary completion 21 January 2027
Study design
Registered phase 3 design and status only
Funding
Sponsor: Amgen

Registry design and status only. No efficacy or safety result from either trial is public.

Read the original source
Company filing, 4 August 2026: MARITIME program ongoing, further phase 3 studies enrolling

Regulatory record

Amgen Inc. earnings release for the second quarter of 2026, filed 4 August 2026 as an exhibit with the U.S. Securities and Exchange Commission.

MARITIME-1 and MARITIME-2 are ongoing, and Amgen lists further phase 3 studies as enrolling: MARITIME-CV (cardiovascular outcomes, NCT07037433, estimated 12,800 participants), MARITIME-HF, MARITIME-OSA-1, MARITIME-OSA-2, MARITIME-SWITCH (from weekly tirzepatide or semaglutide to MariTide every 8 weeks or quarterly), and long-term extensions of MARITIME-1 and MARITIME-2. Amgen also says three phase 3 studies in type 2 diabetes will start in 2026. The release heads the section MariTide (maridebart cafraglutide/AMG 133).

Participants / model
Adults with obesity or overweight and related conditions (planned)
Treatment
Subcutaneous MariTide, monthly, every 8 weeks, or quarterly
Follow-up
Program status as of 4 August 2026
Study design
Company filing (earnings release, SEC exhibit); program status only
Funding
not stated in the source

Program status only. No phase 3 efficacy, safety or outcome data are reported.

Read the original source

How does maridebart cafraglutide work, and how long does it last?

It combines GIP receptor antagonism (the antibody) with GLP-1 receptor agonism (two attached GLP-1 analogue peptides). In the phase 1 study, the mean terminal half-life in people ranged from 14 to 24 days (about 21 days).

The WHO record defines the compound as a fully human anti-human GIPR IgG1-kappa monoclonal antibody conjugated to two identical GLP-1 analogue peptides. The antibody part blocks the GIP receptor, and the attached peptides activate the GLP-1 receptor. The sources reviewed do not describe preclinical results, so nothing further about the mechanism is stated here.

In the phase 1 study in participants with obesity, subcutaneous AMG 133 had a mean terminal half-life of 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6.

WHO Proposed INN List 128 (2022): antibody-peptide conjugate, GIP antagonist and GLP-1 agonist

Chemical identity record

World Health Organization. Proposed International Nonproprietary Names: List 128. WHO Drug Information, Vol. 36, No. 4, 2022. List 133 (Vol. 39, No. 2, 2025) republishes the entry with a replaced chemical name.

Maridebart cafraglutide is defined as a fully human anti-human GIPR IgG1-kappa monoclonal antibody conjugated to two identical GLP-1 analogue peptides, with the stated action GIP receptor antagonist and GLP-1 receptor agonist. It is an antibody-peptide conjugate, not a single peptide, and it antagonizes the GIP receptor. A PubChem name search for maridebart cafraglutide and MariTide returned no compound record on 10 October 2026.

Participants / model
Molecular identity, not a clinical population
Treatment
Antibody-peptide conjugate, subcutaneous
Follow-up
Not applicable
Study design
Official WHO nomenclature record (Proposed INN list)
Funding
not stated in the source

Because the GIP receptor is antagonized, the compound is not a GLP-1 and GIP receptor co-agonist of the kind tirzepatide is.

Read the original source
Phase 1: 75 participants, half-life about 21 days, -14.5% at day 85 in the 420 mg group

Clinical trial

Véniant MM et al. Nat Metab. 2024;6(2):290-303. PMID 38316982.

The paper reports the final analysis of 75 participants in five single-dose and three multiple-dose cohorts. In the 420 mg every-4-weeks multiple-dose group, mean body weight change was -14.5% by day 85 and was still -11.2% 150 days after the last dose. The human mean terminal half-life ranged from 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6. The most common adverse events were nausea and vomiting, mostly mild and resolving within 48 hours, and no severe or serious adverse events or adverse events leading to permanent discontinuation were reported.

Participants / model
Adults with obesity (75 participants in the reported cohorts) at three US sites
Treatment
Subcutaneous AMG 133, single doses of 21 to 840 mg and every-4-weeks multiple doses
Follow-up
Single doses; multiple doses every 4 weeks; follow-up to 150 days after the last dose
Study design
Randomized, double-blind, placebo-controlled single- and multiple-ascending-dose phase 1 trial with preclinical data (NCT04478708)
Funding
not stated in the source

The sources reviewed do not say whether the weight figures are placebo-adjusted.

Read the original source

What adverse events and tolerability findings were reported?

In phase 1, nausea and vomiting were the most common adverse events, mostly mild, and no severe or serious events were reported. In phase 2 the authors report common gastrointestinal events that were less frequent with dose escalation, and Amgen reports gastrointestinal discontinuations of up to 7.8% in the escalation arms.

In the phase 1 study (75 participants) the most common adverse events were nausea and vomiting, mostly mild and resolving within 48 hours. No severe or serious adverse events and no adverse events leading to permanent discontinuation were reported.

In the phase 2 trial the authors report that gastrointestinal adverse events were common, less frequent with dose escalation and a lower starting dose, and that no unexpected safety signals emerged. Amgen's press release of 23 June 2025 reports discontinuation due to gastrointestinal adverse events of up to 7.8% in the dose-escalation arms, lower than in the arms without escalation, and says no new safety signals were identified.

Only the abstract-level safety summary and Amgen's 7.8% figure are given here. The full text of the phase 2 paper was not retrieved, so per-arm nausea, vomiting and discontinuation percentages, heart rate and any bone or lean-mass findings are not reported on this page. No phase 3 safety or cardiovascular outcome data exist.

Phase 1: 75 participants, half-life about 21 days, -14.5% at day 85 in the 420 mg group

Clinical trial

Véniant MM et al. Nat Metab. 2024;6(2):290-303. PMID 38316982.

The paper reports the final analysis of 75 participants in five single-dose and three multiple-dose cohorts. In the 420 mg every-4-weeks multiple-dose group, mean body weight change was -14.5% by day 85 and was still -11.2% 150 days after the last dose. The human mean terminal half-life ranged from 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6. The most common adverse events were nausea and vomiting, mostly mild and resolving within 48 hours, and no severe or serious adverse events or adverse events leading to permanent discontinuation were reported.

Participants / model
Adults with obesity (75 participants in the reported cohorts) at three US sites
Treatment
Subcutaneous AMG 133, single doses of 21 to 840 mg and every-4-weeks multiple doses
Follow-up
Single doses; multiple doses every 4 weeks; follow-up to 150 days after the last dose
Study design
Randomized, double-blind, placebo-controlled single- and multiple-ascending-dose phase 1 trial with preclinical data (NCT04478708)
Funding
not stated in the source

The sources reviewed do not say whether the weight figures are placebo-adjusted.

Read the original source
Phase 2: 592 adults, 52 weeks, -12.3% to -16.2% versus -2.5% (obesity cohort, treatment policy estimand)

Randomized controlled trial

Jastreboff AM et al. N Engl J Med. 2025;393(9):843-857. PMID 40549887.

Obesity cohort (465 participants, 63% female, mean age 47.9, mean BMI 37.9): mean percent change in body weight to week 52, treatment policy estimand, ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) across maridebart cafraglutide regimens versus -2.5% (95% CI -4.2 to -0.7) on placebo. Obesity-with-type 2 diabetes cohort (127 participants): -8.4% (95% CI -11.0 to -5.7) to -12.3% (95% CI -15.3 to -9.2) versus -1.7% (95% CI -2.9 to -0.6), with HbA1c change of -1.2 to -1.6 percentage points versus +0.1 on placebo. The authors report gastrointestinal adverse events were common, less frequent with dose escalation and a lower starting dose, and that no unexpected safety signals emerged.

Participants / model
592 adults with obesity, with and without type 2 diabetes, in two cohorts
Treatment
Subcutaneous maridebart cafraglutide every 4 or 8 weeks: 140, 280 or 420 mg every 4 weeks without dose escalation, 420 mg every 8 weeks, and 420 mg every 4 weeks with 4-week or 12-week dose escalation
Follow-up
52 weeks
Study design
Double-blind, randomized, placebo-controlled, dose-ranging phase 2 trial (NCT05669599)
Funding
Funded by Amgen

The weight figures are mean percent change in body weight by the treatment policy estimand, each arm against its own placebo value, not placebo-adjusted differences. The full text was not retrieved, so only abstract-level safety is given.

Read the original source
Company statement, 23 June 2025: efficacy estimand 16.3% to 19.9%, GI discontinuations up to 7.8%

Regulatory record

Amgen press release dated 23 June 2025, reporting results of the phase 2 MariTide obesity study presented at the American Diabetes Association 85th Scientific Sessions.

By the efficacy estimand, weight change at week 52 ranged from 16.3% to 19.9% with MariTide versus 2.6% on placebo in the obesity cohort, and from 12.1% to 17.0% versus 1.4% in the type 2 diabetes cohort. Amgen reports discontinuation due to gastrointestinal adverse events in the dose-escalation arms of up to 7.8%, lower than in the arms without escalation, and says no new safety signals were identified. The treatment policy numbers in the release match the New England Journal of Medicine paper. Amgen's footnote defines the efficacy estimand as the effect had participants adhered for the full 52 weeks (missing data after early discontinuation are estimated from individual response) and the treatment policy estimand as the intent-to-treat analysis, so the efficacy figures are the larger ones.

Participants / model
Adults with obesity, with and without type 2 diabetes
Treatment
Subcutaneous MariTide, 52 weeks
Follow-up
52 weeks
Study design
Company press release on the phase 2 trial; not peer reviewed
Funding
not stated in the source

The efficacy estimand figures are larger than the treatment policy figures in the paper because the efficacy estimand models full adherence. They are company-reported and are not placebo-adjusted.

Read the original source

Why does maridebart cafraglutide sit in B tier?

The evidence is one randomized phase 2 trial in 592 people published in the New England Journal of Medicine and a phase 1 paper, with a phase 3 program that has not reported. It is not A because no phase 3 result exists.

The phase 2 result is 12.3% to 16.2% weight loss at 52 weeks against 2.5% on placebo (obesity cohort, treatment policy estimand, change from baseline), and the phase 1 paper gives a human half-life of about 21 days. The phase 3 program is nearly 5,000 enrolled participants in the two weight-management trials (3,853 plus 1,105) and an estimated 12,800-participant cardiovascular outcomes trial, none of which has reported.

The mechanism is unusual: GIP receptor antagonism plus GLP-1 agonism. Gastrointestinal events were less frequent with dose escalation, and Amgen reports gastrointestinal discontinuations of up to 7.8% even in the escalation arms. Later regimens (every 8 weeks, quarterly) and the extension and type 2 diabetes phase 2 results rest on company statements.

Phase 2: 592 adults, 52 weeks, -12.3% to -16.2% versus -2.5% (obesity cohort, treatment policy estimand)

Randomized controlled trial

Jastreboff AM et al. N Engl J Med. 2025;393(9):843-857. PMID 40549887.

Obesity cohort (465 participants, 63% female, mean age 47.9, mean BMI 37.9): mean percent change in body weight to week 52, treatment policy estimand, ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) across maridebart cafraglutide regimens versus -2.5% (95% CI -4.2 to -0.7) on placebo. Obesity-with-type 2 diabetes cohort (127 participants): -8.4% (95% CI -11.0 to -5.7) to -12.3% (95% CI -15.3 to -9.2) versus -1.7% (95% CI -2.9 to -0.6), with HbA1c change of -1.2 to -1.6 percentage points versus +0.1 on placebo. The authors report gastrointestinal adverse events were common, less frequent with dose escalation and a lower starting dose, and that no unexpected safety signals emerged.

Participants / model
592 adults with obesity, with and without type 2 diabetes, in two cohorts
Treatment
Subcutaneous maridebart cafraglutide every 4 or 8 weeks: 140, 280 or 420 mg every 4 weeks without dose escalation, 420 mg every 8 weeks, and 420 mg every 4 weeks with 4-week or 12-week dose escalation
Follow-up
52 weeks
Study design
Double-blind, randomized, placebo-controlled, dose-ranging phase 2 trial (NCT05669599)
Funding
Funded by Amgen

The weight figures are mean percent change in body weight by the treatment policy estimand, each arm against its own placebo value, not placebo-adjusted differences. The full text was not retrieved, so only abstract-level safety is given.

Read the original source
Phase 1: 75 participants, half-life about 21 days, -14.5% at day 85 in the 420 mg group

Clinical trial

Véniant MM et al. Nat Metab. 2024;6(2):290-303. PMID 38316982.

The paper reports the final analysis of 75 participants in five single-dose and three multiple-dose cohorts. In the 420 mg every-4-weeks multiple-dose group, mean body weight change was -14.5% by day 85 and was still -11.2% 150 days after the last dose. The human mean terminal half-life ranged from 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6. The most common adverse events were nausea and vomiting, mostly mild and resolving within 48 hours, and no severe or serious adverse events or adverse events leading to permanent discontinuation were reported.

Participants / model
Adults with obesity (75 participants in the reported cohorts) at three US sites
Treatment
Subcutaneous AMG 133, single doses of 21 to 840 mg and every-4-weeks multiple doses
Follow-up
Single doses; multiple doses every 4 weeks; follow-up to 150 days after the last dose
Study design
Randomized, double-blind, placebo-controlled single- and multiple-ascending-dose phase 1 trial with preclinical data (NCT04478708)
Funding
not stated in the source

The sources reviewed do not say whether the weight figures are placebo-adjusted.

Read the original source
Registry: MARITIME-1 and MARITIME-2, Amgen sponsor, Active not recruiting, no posted results

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Record NCT06858839 (MARITIME-1), with record NCT06858878 (MARITIME-2). Read on 10 October 2026.

ClinicalTrials.gov lists Amgen as sponsor of MARITIME-1 with the intervention maridebart cafraglutide and the other names AMG 133 and MariTide. MARITIME-1: adults without type 2 diabetes, 3,853 participants enrolled, primary endpoint percent change in body weight at week 72, status Active, not recruiting, start 12 March 2025, estimated primary completion 21 January 2027. MARITIME-2 (NCT06858878): adults with type 2 diabetes, 1,105 enrolled, same endpoint and primary completion date, status Active, not recruiting. Neither record has posted results. A registration without posted results is not an outcome.

Participants / model
Adults with obesity or overweight, without and with type 2 diabetes (planned)
Treatment
Subcutaneous maridebart cafraglutide versus placebo, 72 weeks
Follow-up
72 weeks per participant; estimated primary completion 21 January 2027
Study design
Registered phase 3 design and status only
Funding
Sponsor: Amgen

Registry design and status only. No efficacy or safety result from either trial is public.

Read the original source
Company statement, 23 June 2025: efficacy estimand 16.3% to 19.9%, GI discontinuations up to 7.8%

Regulatory record

Amgen press release dated 23 June 2025, reporting results of the phase 2 MariTide obesity study presented at the American Diabetes Association 85th Scientific Sessions.

By the efficacy estimand, weight change at week 52 ranged from 16.3% to 19.9% with MariTide versus 2.6% on placebo in the obesity cohort, and from 12.1% to 17.0% versus 1.4% in the type 2 diabetes cohort. Amgen reports discontinuation due to gastrointestinal adverse events in the dose-escalation arms of up to 7.8%, lower than in the arms without escalation, and says no new safety signals were identified. The treatment policy numbers in the release match the New England Journal of Medicine paper. Amgen's footnote defines the efficacy estimand as the effect had participants adhered for the full 52 weeks (missing data after early discontinuation are estimated from individual response) and the treatment policy estimand as the intent-to-treat analysis, so the efficacy figures are the larger ones.

Participants / model
Adults with obesity, with and without type 2 diabetes
Treatment
Subcutaneous MariTide, 52 weeks
Follow-up
52 weeks
Study design
Company press release on the phase 2 trial; not peer reviewed
Funding
not stated in the source

The efficacy estimand figures are larger than the treatment policy figures in the paper because the efficacy estimand models full adherence. They are company-reported and are not placebo-adjusted.

Read the original source
Company filing, 4 August 2026: MARITIME program ongoing, further phase 3 studies enrolling

Regulatory record

Amgen Inc. earnings release for the second quarter of 2026, filed 4 August 2026 as an exhibit with the U.S. Securities and Exchange Commission.

MARITIME-1 and MARITIME-2 are ongoing, and Amgen lists further phase 3 studies as enrolling: MARITIME-CV (cardiovascular outcomes, NCT07037433, estimated 12,800 participants), MARITIME-HF, MARITIME-OSA-1, MARITIME-OSA-2, MARITIME-SWITCH (from weekly tirzepatide or semaglutide to MariTide every 8 weeks or quarterly), and long-term extensions of MARITIME-1 and MARITIME-2. Amgen also says three phase 3 studies in type 2 diabetes will start in 2026. The release heads the section MariTide (maridebart cafraglutide/AMG 133).

Participants / model
Adults with obesity or overweight and related conditions (planned)
Treatment
Subcutaneous MariTide, monthly, every 8 weeks, or quarterly
Follow-up
Program status as of 4 August 2026
Study design
Company filing (earnings release, SEC exhibit); program status only
Funding
not stated in the source

Program status only. No phase 3 efficacy, safety or outcome data are reported.

Read the original source
Searches, 10 October 2026: no US application or label, no phase 3 result

PubMed search record

PubMed search for maridebart cafraglutide, run on 10 October 2026 (14 records). ClinicalTrials.gov search for maridebart OR MariTide OR AMG-133 run the same day (29 records). openFDA Drugs@FDA and DailyMed searches run the same day.

No US approval exists: on 10 October 2026 openFDA Drugs@FDA returned no application records for maridebart cafraglutide and a DailyMed search returned no labels. A PubMed search the same day returned 14 records: the phase 2 trial paper, three correspondence items on it, the phase 1 paper, one mouse study, seven reviews and one unrelated bariatric surgery audit. None reports a phase 3 result. A ClinicalTrials.gov search for maridebart OR MariTide OR AMG-133 returned 29 records (15 phase 1, 3 phase 2, 11 phase 3); the only posted results are for two phase 1 studies (NCT04478708 and NCT05056246), and no MARITIME trial has posted results.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Literature, registry and regulator searches
Funding
not stated in the source

A search result shows what the databases returned on that date. Only US regulator databases were searched. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

WHO Proposed INN List 128 (2022): antibody-peptide conjugate, GIP antagonist and GLP-1 agonist

Chemical identity record

World Health Organization. Proposed International Nonproprietary Names: List 128. WHO Drug Information, Vol. 36, No. 4, 2022. List 133 (Vol. 39, No. 2, 2025) republishes the entry with a replaced chemical name.

Maridebart cafraglutide is defined as a fully human anti-human GIPR IgG1-kappa monoclonal antibody conjugated to two identical GLP-1 analogue peptides, with the stated action GIP receptor antagonist and GLP-1 receptor agonist. It is an antibody-peptide conjugate, not a single peptide, and it antagonizes the GIP receptor. A PubChem name search for maridebart cafraglutide and MariTide returned no compound record on 10 October 2026.

Participants / model
Molecular identity, not a clinical population
Treatment
Antibody-peptide conjugate, subcutaneous
Follow-up
Not applicable
Study design
Official WHO nomenclature record (Proposed INN list)
Funding
not stated in the source

Because the GIP receptor is antagonized, the compound is not a GLP-1 and GIP receptor co-agonist of the kind tirzepatide is.

Read the original source
Registry: MARITIME-1 and MARITIME-2, Amgen sponsor, Active not recruiting, no posted results

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Record NCT06858839 (MARITIME-1), with record NCT06858878 (MARITIME-2). Read on 10 October 2026.

ClinicalTrials.gov lists Amgen as sponsor of MARITIME-1 with the intervention maridebart cafraglutide and the other names AMG 133 and MariTide. MARITIME-1: adults without type 2 diabetes, 3,853 participants enrolled, primary endpoint percent change in body weight at week 72, status Active, not recruiting, start 12 March 2025, estimated primary completion 21 January 2027. MARITIME-2 (NCT06858878): adults with type 2 diabetes, 1,105 enrolled, same endpoint and primary completion date, status Active, not recruiting. Neither record has posted results. A registration without posted results is not an outcome.

Participants / model
Adults with obesity or overweight, without and with type 2 diabetes (planned)
Treatment
Subcutaneous maridebart cafraglutide versus placebo, 72 weeks
Follow-up
72 weeks per participant; estimated primary completion 21 January 2027
Study design
Registered phase 3 design and status only
Funding
Sponsor: Amgen

Registry design and status only. No efficacy or safety result from either trial is public.

Read the original source
Phase 1: 75 participants, half-life about 21 days, -14.5% at day 85 in the 420 mg group

Clinical trial

Véniant MM et al. Nat Metab. 2024;6(2):290-303. PMID 38316982.

The paper reports the final analysis of 75 participants in five single-dose and three multiple-dose cohorts. In the 420 mg every-4-weeks multiple-dose group, mean body weight change was -14.5% by day 85 and was still -11.2% 150 days after the last dose. The human mean terminal half-life ranged from 14 to 24 days (about 21 days), with peak concentrations by day 4 to 6. The most common adverse events were nausea and vomiting, mostly mild and resolving within 48 hours, and no severe or serious adverse events or adverse events leading to permanent discontinuation were reported.

Participants / model
Adults with obesity (75 participants in the reported cohorts) at three US sites
Treatment
Subcutaneous AMG 133, single doses of 21 to 840 mg and every-4-weeks multiple doses
Follow-up
Single doses; multiple doses every 4 weeks; follow-up to 150 days after the last dose
Study design
Randomized, double-blind, placebo-controlled single- and multiple-ascending-dose phase 1 trial with preclinical data (NCT04478708)
Funding
not stated in the source

The sources reviewed do not say whether the weight figures are placebo-adjusted.

Read the original source
Phase 2: 592 adults, 52 weeks, -12.3% to -16.2% versus -2.5% (obesity cohort, treatment policy estimand)

Randomized controlled trial

Jastreboff AM et al. N Engl J Med. 2025;393(9):843-857. PMID 40549887.

Obesity cohort (465 participants, 63% female, mean age 47.9, mean BMI 37.9): mean percent change in body weight to week 52, treatment policy estimand, ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) across maridebart cafraglutide regimens versus -2.5% (95% CI -4.2 to -0.7) on placebo. Obesity-with-type 2 diabetes cohort (127 participants): -8.4% (95% CI -11.0 to -5.7) to -12.3% (95% CI -15.3 to -9.2) versus -1.7% (95% CI -2.9 to -0.6), with HbA1c change of -1.2 to -1.6 percentage points versus +0.1 on placebo. The authors report gastrointestinal adverse events were common, less frequent with dose escalation and a lower starting dose, and that no unexpected safety signals emerged.

Participants / model
592 adults with obesity, with and without type 2 diabetes, in two cohorts
Treatment
Subcutaneous maridebart cafraglutide every 4 or 8 weeks: 140, 280 or 420 mg every 4 weeks without dose escalation, 420 mg every 8 weeks, and 420 mg every 4 weeks with 4-week or 12-week dose escalation
Follow-up
52 weeks
Study design
Double-blind, randomized, placebo-controlled, dose-ranging phase 2 trial (NCT05669599)
Funding
Funded by Amgen

The weight figures are mean percent change in body weight by the treatment policy estimand, each arm against its own placebo value, not placebo-adjusted differences. The full text was not retrieved, so only abstract-level safety is given.

Read the original source
Company statement, 23 June 2025: efficacy estimand 16.3% to 19.9%, GI discontinuations up to 7.8%

Regulatory record

Amgen press release dated 23 June 2025, reporting results of the phase 2 MariTide obesity study presented at the American Diabetes Association 85th Scientific Sessions.

By the efficacy estimand, weight change at week 52 ranged from 16.3% to 19.9% with MariTide versus 2.6% on placebo in the obesity cohort, and from 12.1% to 17.0% versus 1.4% in the type 2 diabetes cohort. Amgen reports discontinuation due to gastrointestinal adverse events in the dose-escalation arms of up to 7.8%, lower than in the arms without escalation, and says no new safety signals were identified. The treatment policy numbers in the release match the New England Journal of Medicine paper. Amgen's footnote defines the efficacy estimand as the effect had participants adhered for the full 52 weeks (missing data after early discontinuation are estimated from individual response) and the treatment policy estimand as the intent-to-treat analysis, so the efficacy figures are the larger ones.

Participants / model
Adults with obesity, with and without type 2 diabetes
Treatment
Subcutaneous MariTide, 52 weeks
Follow-up
52 weeks
Study design
Company press release on the phase 2 trial; not peer reviewed
Funding
not stated in the source

The efficacy estimand figures are larger than the treatment policy figures in the paper because the efficacy estimand models full adherence. They are company-reported and are not placebo-adjusted.

Read the original source
Company statement, 3 February 2026: Part 2 extension and type 2 diabetes phase 2, no numbers

Regulatory record

Amgen Inc. earnings release for the fourth quarter of 2025, dated 3 February 2026, filed as an exhibit with the U.S. Securities and Exchange Commission.

Part 2 of the phase 2 study, an exploratory 52-week extension in people who lost at least 15% of body weight in Part 1, is complete: the large majority kept their weight loss for an additional 52 weeks on a lower monthly dose or a quarterly dose, with a very low incidence of nausea and vomiting and no new safety signals. A separate phase 2 study in type 2 diabetes (NCT06660173) reached its 24-week point with reductions in HbA1c and weight and a safety profile Amgen calls consistent with the GLP-1 class. Neither result has a published paper or a number in the records reviewed.

Participants / model
Adults who lost at least 15% in Part 1; adults with type 2 diabetes
Treatment
Subcutaneous MariTide, lower monthly or quarterly doses
Follow-up
52-week extension; 24 weeks in the type 2 diabetes study
Study design
Company earnings release; not peer reviewed, and no numbers given
Funding
not stated in the source

Company statement without numbers. No paper for either result was found in the records reviewed.

Read the original source
Company filing, 4 August 2026: MARITIME program ongoing, further phase 3 studies enrolling

Regulatory record

Amgen Inc. earnings release for the second quarter of 2026, filed 4 August 2026 as an exhibit with the U.S. Securities and Exchange Commission.

MARITIME-1 and MARITIME-2 are ongoing, and Amgen lists further phase 3 studies as enrolling: MARITIME-CV (cardiovascular outcomes, NCT07037433, estimated 12,800 participants), MARITIME-HF, MARITIME-OSA-1, MARITIME-OSA-2, MARITIME-SWITCH (from weekly tirzepatide or semaglutide to MariTide every 8 weeks or quarterly), and long-term extensions of MARITIME-1 and MARITIME-2. Amgen also says three phase 3 studies in type 2 diabetes will start in 2026. The release heads the section MariTide (maridebart cafraglutide/AMG 133).

Participants / model
Adults with obesity or overweight and related conditions (planned)
Treatment
Subcutaneous MariTide, monthly, every 8 weeks, or quarterly
Follow-up
Program status as of 4 August 2026
Study design
Company filing (earnings release, SEC exhibit); program status only
Funding
not stated in the source

Program status only. No phase 3 efficacy, safety or outcome data are reported.

Read the original source

Why is Maridebart cafraglutide in B tier?

B fits a compound with one well-run randomized phase 2 trial in the New England Journal of Medicine, a phase 1 paper, and a large phase 3 program that has not reported. The phase 2 weight effect is 12.3% to 16.2% at 52 weeks against 2.5% on placebo, with gastrointestinal events that were less frequent with dose escalation. It is not A because no phase 3 result exists and no regulator has approved it.