A new long-acting obesity drug may offer a simpler path to weight loss, with results rivaling weekly treatments. In a Phase 2 clinical trial, the experimental medication maridebart cafraglutide—also known as MariTide—was shown to induce substantial weight loss with just once-monthly injections, in both patients with obesity and those with type 2 diabetes.
“This was an intriguing finding,” said Dr. Ania Jastreboff, principal investigator and director of Yale’s Obesity Research Center. “Usually with medications in this class, we observe less weight reduction in patients with obesity and type 2 diabetes than in those who have obesity alone. In this study, the discrepancy was not as large as we usually observe.”
A dual-action strategy
MariTide is a peptide–antibody conjugate that uniquely combines two mechanisms: it activates the GLP-1 receptor and blocks the GIP receptor. Both hormonal pathways are involved in regulating appetite and glucose levels. This dual approach is thought to improve blood sugar control while enhancing weight loss by acting on brain centers related to hunger and satiety.
Results from the Phase 2 trial
The randomized, placebo-controlled study included 592 adults: 465 with obesity alone, and 127 with both obesity and type 2 diabetes. Participants received MariTide subcutaneously every 4 or 8 weeks at various dosages, or placebo, over 52 weeks. Key findings included:
- Up to 16.2% body weight loss in the obesity-only group
- Up to 12.3% body weight loss in the obesity–diabetes group
- Hemoglobin A1c reductions of 1.2–1.6 percentage points in patients with diabetes
Placebo recipients lost only 2.5% and 1.7% of body weight in the respective groups, underscoring the drug’s substantial effect. Importantly, a more gradual dose escalation led to fewer gastrointestinal side effects like nausea, vomiting, and diarrhea—issues common to GLP-1 receptor agonists.
Implications for treatment and adherence
Most currently approved anti-obesity medications—including Wegovy and Zepbound—require weekly dosing. A longer-acting option could significantly improve patient adherence and outcomes.
“The ability to dose once monthly may reduce the burden on patients and improve real-world effectiveness,” Jastreboff said. Her team is now leading a Phase 3 trial (MARITIME-1) to further evaluate once-monthly MariTide under clinical conditions.
Obesity affects over 42% of U.S. adults and is closely linked to type 2 diabetes and cardiovascular disease. As next-generation drugs like MariTide move toward potential approval, they offer new hope for treating what remains one of the nation’s most pressing health challenges.
Journal: The New England Journal of Medicine
DOI: 10.1056/NEJMoa2504214
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