Results from a Phase II clinical trial (NCT05669599) evaluating the novel therapy MariTide (maridebart cafraglutide; Amgen) showed significant and sustained weight loss in adults with obesity both with or without type 2 diabetes.^1,2

Once-Monthly MariTide Shows Promising Weight Loss Results in Obesity and Type 2 Diabetes Patients

The findings, also published by The New England Journal of Medicine (NEJM), show the drug’s potential to become a durable, lower-burden treatment for obesity and metabolic disease, pending confirmation in ongoing Phase III trials, according to trial investigators.³

"MariTide delivered strong efficacy, including sustained weight loss without a plateau in the 52-week Phase II study and meaningful improvements in cardiometabolic risk factors, representing a defining advance for the obesity field," Jay Bradner, MD, executive vice president of Research and Development at Amgen, said in a press release. "These results, alongside the Phase I Pharmacokinetics Low Dose Initiation data, have shaped our Phase III MARITIME program. MariTide's monthly or less frequent dosing has the potential to improve adherence and long-term weight control, providing the opportunity to optimize health outcomes for people living with obesity, type 2 diabetes and related conditions."¹

How Does MariTide Compare to Other GLP-1 Medications?

MariTide is a bispecific molecule produced by conjugating a fully human monoclonal anti-human GIPR antagonist antibody to two GLP-1 analogue agonist peptides using amino acid linkers. Results from a Phase I trial (NCT04478708) indicated the drug produced longer lasting and durable reductions in body weight compared to the popular GLP-1 agonists currently on the market: Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s Zepbound (tirzepatide).⁴

“Although both GIP receptor agonism and antagonism lead to weight reduction, especially when combined with GLP-1 receptor agonism, genetic evidence indicates that GIP receptor variants that are linked to reduced receptor signaling are associated with a lower body-mass index,” the study authors wrote in NEJM. “Maridebart cafraglutide, composed of two identical GLP-1 peptide analogues conjugated to a single monoclonal antibody antagonist to the GIP receptor, has a half-life of approximately 21 days (approximately 3 times as long as the longest-acting Food and Drug Administration–approved once-weekly medications for obesity), which supports monthly or less frequent administration.”³

MariTide Phase II Trial Design and Dosing

• The current, double-blind, randomized, placebo-controlled, dose-ranging trial enrolled 592 participants, who were divided into 11 groups as two cohorts comprised of those with obesity or those with obesity and type 2 diabetes.
• Patients with obesity (n = 465) were randomly assigned in a 3:3:3:2:2:2:3 ratio to receive subcutaneous (SC) MariTide at a dose of 140, 280, or 420 mg every four weeks without dose escalation; 420 mg every eight weeks without dose escalation; 420 mg every four weeks with four-week dose escalation; 420 mg every four weeks with 12-week dose escalation; or placebo.
• Patients with both obesity and type 2 diabetes (n = 127) were randomly assigned in a 1:1:1:1 ratio to receive SC MariTide at a dose of 140, 280, or 420 mg every four weeks without dose escalation or placebo.
• The trial’s primary endpoint was percent change in body weight from baseline to week 52.

MariTide Phase II Trial Shows Up to 20% Weight Loss in Obesity and Type 2 Diabetes Patients

• Results from the obesity cohort show a mean percent change in body weight from baseline to week 52 ranged from −12.3% (95% confidence interval [CI], −15.0 to −9.7) to −16.2% (95% CI, −18.9 to −13.5) among those administered MariTide versus −2.5% (95% CI, −4.2 to −0.7) among those administered placebo.
• Results from the obesity–diabetes cohort show a mean percent change in body weight from baseline to week 52 that ranged from −8.4% (95% CI, −11.0 to −5.7) to −12.3% (95% CI, −15.3 to −9.2) among those administered MariTide versus −1.7% (95% CI, −2.9 to −0.6) among those administered placebo.
• Mean change in glycated hemoglobin level in the obesity–diabetes cohort was −1.2 to −1.6 percentage points among those administered MariTide compared to 0.1 percentage points among those administered placebo.
• In total, investigators reported average weight loss of approximately 20% among patients with obesity without type 2 diabetes in the MariTide cohort compared to 2.6% in the placebo cohort.
• Among patients with obesity with type 2 diabetes, investigators reported average weight loss of up to approximately 17% compared to 1.4% in the placebo cohort, per the efficacy estimand.¹

MariTide Safety Profile and Implications for Phase III MARITIME Program

• In terms of safety, gastrointestinal adverse events were common among those administered MariTide but occurred less frequently with dose escalation and a lower starting dose, according to the trial investigators.
• There were no new or unexpected safety signals reported.

“A consistent observation from clinical trials with nutrient-stimulated hormone receptor modulators is that persons with obesity and type 2 diabetes lose less weight than those without type 2 diabetes; the mechanisms of the response are unknown,” the study authors concluded. “We found that participants with type 2 diabetes lost only slightly less weight than those without type 2 diabetes (differences of approximately 3 to 4 percentage points between the obesity cohort and the obesity–diabetes cohort). Participants in the obesity–diabetes cohort lost on average up to 12% of body weight on the basis of the treatment policy estimand (up to 17% on the basis of the efficacy estimand), with few agents to date resulting in such a magnitude of reduction in persons with type 2 diabetes and none that are administered once monthly.”³

References

1. Results From Amgen's Phase 2 Obesity Study of Monthly Maritide Presented at the American Diabetes Association 85th Scientific Sessions. News release. Amgen. June 23, 2025. Accessed June 23, 2025. https://www.prnewswire.com/news-releases/results-from-amgens-phase-2-obesity-study-of-monthly-maritide-presented-at-the-american-diabetes-association-85th-scientific-sessions-302487811.html

2. Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Subjects With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus. ClinicalTrials.gov. Updated February 20, 2025. Accessed June 23, 2025. https://clinicaltrials.gov/study/NCT05669599

3. Jastreboff A., et al. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial. N Engl J Med 2025. doi/full/10.1056/NEJMoa2504214

4. Véniant, M.M., et al. A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat Metab 2024. https://doi.org/10.1038/s42255-023-00966-w