26 June 2025
Category: Clinical Trial I Obesity & Metabolic Disorders I
Diabetes and Weight loss
Written and Reviewed By:
Vikas Londhe, MPharm
In recent times, the focus has been shifted to next-generation metabolic therapies and innovative molecules that target the body’s hormonal cascades that are involved in hunger, energy burning, and fat storage. Among them, GLP-1 receptor agonists and GIP-based therapies have improved metabolic health. In this space, Amgen made a bold move into weight loss and diabetes treatments with the development of the maridebart-cafraglutide combination branded as MariTide. Amgen released positive Phase 2 results from their Maritime‑1 trial, and the results are published in the New England Journal of Medicine.
MariTide represents first-in-class dual-action molecules, combining glucagon-like peptide-1 (GLP-1) receptor agonism with glucose-dependent insulinotropic polypeptide (GIP) receptor antagonism potential with a synergistic mechanism that modulates insulin sensitivity and lipid metabolism. MariTide is designed to be administered as a once-monthly subcutaneous dose, which will increase patient compliance and convenience. The trial’s results showing up to 20% body weight reduction position MariTide as a major breakthrough in the near future.
Phase 2 Maritime‑1 Trial
The Phase 2 MARITIME-1 trial was a randomized, double-blind, placebo-controlled, dose-ranging study evaluating maridebart cafraglutide (MariTide) in adults with obesity or overweight who had at least one weight-related comorbidity. A total of 592 participants were enrolled into two cohorts: 465 in the obesity cohort (BMI ≥30 or ≥27 with complications, HbA1c <6.5%) and 127 in the obesity–diabetes cohort (BMI ≥27, HbA1c 7–<10%). Participants received subcutaneous MariTide every 4 or 8 weeks for 52 weeks across varying doses (140, 280, or 420 mg), with or without dose escalation, or placebo. The study assessed weight loss efficacy, metabolic improvements, and safety outcomes.
Endpoints
The primary endpoint was the percentage change in body weight from baseline to week 52. Secondary endpoints included proportions achieving ≥5% to ≥20% weight loss and changes in waist circumference, HbA1c, lipid profiles, CRP, and blood pressure. Safety outcomes focused on gastrointestinal adverse events and treatment discontinuation. The study aimed to evaluate both the weight loss efficacy and broader metabolic benefits of maridebart cafraglutide (MariTide).
Results
In the obesity cohort, maridebart cafraglutide led to a mean body weight reduction of −16.3% to −19.9% (efficacy estimand) compared to 2.6% with placebo. In the obesity–diabetes cohort, reductions ranged from −12.1% to −17.0% compared to 1.4% with placebo. More participants achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss with maridebart cafraglutide. Additionally, significant HbA1c reduction and improvements in waist circumference, blood pressure, hs-CRP, and lipid profiles were observed.
Side Effects
In the phase 2 trial, 90–99% (obesity) and 91–97% (obesity–diabetes) of participants on maridebart cafraglutide reported at least one adverse event, versus 68% and 81% with placebo, respectively. Gastrointestinal events (nausea, vomiting, retching and diarrhea) were most common and mostly mild to moderate, with higher rates in no-dose-escalation groups. Discontinuation due to GI events occurred in up to 27% of participants. There were 35 serious adverse events and 2 deaths, both deemed unrelated to treatment.
In the phase 2 trial, maridebart cafraglutide was associated with mild-to-moderate hypersensitivity (5%), increased gallbladder events, and a few cases of level 2 hypoglycemia. Minor mood events, slight increases in heart rate, amylase, lipase, and calcitonin (within normal range), and decreased liver aminotransferase levels were noted. No cases of pancreatitis, diabetic retinopathy, or C-cell hyperplasia occurred.
Mechanism of Action
Maridebart cafraglutide works through a unique combination of actions. It blocks the GIP receptor and activates the GLP-1 receptor using two attached GLP-1 agonist peptides (cafraglutide), which together regulate body weight. This combination helps people feel full for longer, slows the emptying of food from the stomach, and reduces hunger, leading to lower calorie intake. It also improves how the body responds to insulin and controls blood sugar levels, making it useful for people with obesity.
Strategic Phase 3 Maritime Design
Amgen’s MARITIME Phase 3 program is currently in progress, consisting of 72-week chronic weight management studies evaluating maridebart cafraglutide (MariTide). The program includes two parallel trials: Maritime 1, enrolling participants with obesity or overweight with at least one weight-related comorbidity, and Maritime 2, targeting individuals with type 2 diabetes. Additional Phase 3 trials evaluating MariTide in patients with atherosclerotic cardiovascular disease, heart failure, and obstructive sleep apnea are expected to launch in 2025. Initial readouts from the ongoing Phase 3 studies are anticipated in 2027, positioning MariTide as a major therapeutic option in obesity and diabetic care.
Bottom Line
Susan Sweeney, executive vice president of Obesity and Related Conditions at Amgen, said, “Obesity affects all parts of the world and people of all different populations, and the challenge is significant.”
We have witnessed a lot of patients in our surroundings, including society, friends, or family; for them, Maridebart Cafraglutide (MariTide) represents a promising new candidate in the competitive market of obesity and metabolic disease treatment. This is backed by robust Phase 2 results showing significant weight loss, metabolic improvements, and a manageable safety profile. MariTide showed the potential to offer meaningful clinical benefits with a once-monthly dosing regimen. At the bottom line, Amgen’s MariTide could redefine long-acting obesity treatment with its potent efficacy, broad metabolic impact, and patient-friendly dosing.
Reference
Jastreboff AM, Ryan DH, Bays HE et al, Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial, The New England Journal of Medicine, Published June 23, 2025, DOI: 10.1056/NEJMoa2504214
Results from Amgen’s phase 2 obesity study of monthly Maritide presented at the American diabetes association 85th scientific sessions, Amgen, https://www.amgen.com/newsroom/press-releases/2025/06/results-from-amgens-phase-2-obesity-study-of-monthly-maritide-presented-at-the-american-diabetes-association-85th-scientific-sessions
Inside Amgen’s Phase 3 MARITIME Program: Advancing the Future of Obesity Care, Amgen, https://www.amgen.com/stories/2025/06/inside-amgens-phase-3-maritime-program—advancing-the-future-of-obesity-care
Maridebart Cafraglutide for Chronic Weight Management, iClinique, https://www.icliniq.com/articles/drug-and-supplements/maridebart-cafraglutide#how-does-maridebart-cafraglutide-work-in-obesity-management
Efficacy and Safety of Maridebart Cafraglutide in Adult Participants with Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-2), ClinicalTrials.gov ID NCT06858878, https://clinicaltrials.gov/study/NCT06858878
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