Once-Monthly Maridebart Cafraglutide Demonstrates Substantial Weight Loss in Phase 2 Trial.

A phase 2 trial published in the New England Journal of Medicine evaluated maridebart cafraglutide (MariTide), a long-acting peptide–antibody conjugate combining GLP-1 receptor agonism and GIP receptor antagonism, administered once monthly or less frequently for obesity management.

The study enrolled 592 adults with obesity, including 127 with type 2 diabetes. In the obesity cohort, the mean body weight reduction at 52 weeks ranged from −12.3% to −16.2% (treatment policy estimand) and up to −19.9% (efficacy estimand), compared with −2.5% with placebo. In the obesity–diabetes cohort, weight loss ranged from −8.4% to −12.3% (treatment policy estimand) and up to −17.0% (efficacy estimand), versus −1.7% with placebo. HbA1c reduction reached −1.2 to −1.6 percentage points in the diabetes group, compared with +0.1% in placebo.

Exploratory analyses showed significant reductions in fat mass (up to −36.8%) and improvements in waist circumference, blood pressure, hs-CRP, and lipid variables. Among participants with prediabetes, 70–95% reverted to normoglycemia with maridebart cafraglutide, versus 17% with placebo.

Gastrointestinal adverse events (nausea, vomiting, constipation, diarrhea) were the most frequent, particularly in groups without dose escalation, leading to discontinuation in up to 27%. Initiating therapy with lower starting doses and gradual escalation reduced discontinuations and improved tolerability. No unexpected safety signals emerged; two deaths occurred but were judged unrelated to the drug.

These findings suggest maridebart cafraglutide could represent a next-generation, less frequent injectable therapy for obesity, with efficacy comparable or superior to weekly GLP-1–based treatments. Ongoing phase 3 trials will determine its long-term safety, durability of effect, and potential role in clinical practice.

#obesity #GLP1 #MaridebartCafraglutide #endocrinology #clinicaltrials

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