Abstract Aim Mazdutide, an agonist of glucagon‐like peptide‐1 and glucagon receptors, significantly reduced weight in early phase trials at doses up to 10 mg. This randomized, double‐blind, placebo‐controlled Phase 1 trial evaluated the safety and efficacy of mazdutide up to 16 mg in adults with overweight or obesity. Materials and Methods Thirty‐two adults with overweight/obesity without diabetes received once‐weekly subcutaneous injections of mazdutide ( n = 24) or placebo ( n = 8) for 20 weeks. Two mazdutide dose escalation regimens (Cohorts 1 and 2, n = 12 each) were used to reach a 16‐mg target dose. Data were analysed using descriptive statistics and mixed model repeated measures to estimate least square means with standard error (SE). Results At Week 20, mean percent change from baseline in body weight was −20.0% (SE: 1.9) for Cohort 1 and −21.0% (1.2) for Cohort 2 versus −0.1% (1.5) for placebo ( p < 0.001). Weight loss of ≥15% was achieved by 66.7% of Cohort 1 and 75.0% of Cohort 2. No placebo participants achieved ≥5% weight loss. Mean percent change in waist circumference was −12.0% (SE: 1.7) in Cohort 1 and −17.0% (1.7) in Cohort 2 versus −0.8% (2.1) in placebo ( p < 0.001). Improved fasting metabolic biomarker profiles and reduced appetite were associated with mazdutide treatment. No serious adverse events (AEs) were reported, and the most common AEs were mild or moderate gastrointestinal disorders. Conclusions Mazdutide at 16 mg was well tolerated and associated with greater weight loss at higher doses than previously studied and improved metabolic regulation in adults with overweight or obesity. US Clinical Trials Registry: NCT05623839.
Bhattachar et al. (Wed,) studied this question.