A Twelve-Week Trial of MET097—A Potent and Ultra-Long-Acting GLP-1 Receptor Agonist

Introduction and Objective: MET097 is a fully biased, ultra-long acting glucagon-like peptide-1 receptor agonist (GLP-1RA). In Ph1, subcutaneous administration of 5 once-weekly doses of MET097 resulted in mean weight loss of up to 7.5%, which persisted 8 weeks after the last dose. Here, the efficacy and tolerability of MET097 were evaluated over 12 weeks. Methods: A Ph2, multicenter, randomized, double-blind, placebo (PBO)-controlled trial enrolled adults with overweight/obesity (BMI 27-38 kg/m²). The primary endpoint was percent change in baseline body weight at Day 85, analyzed using MMRM. Participants were randomized to once-weekly MET097 or PBO in five dosing cohorts: four titration-free groups (0.6, 0.8, 1.0, 1.2 mg) and one dose-escalation group (0.4/0.8/1.2 mg each taken for 4 weeks). Results: A total of 120 participants had a mean age of 41 yrs, mean BMI of 31.2 kg/m2, and were ~52% female. Most common AEs were GI-related (nausea, vomiting, constipation, and diarrhea), generally dose dependent, and mild/moderate. The dose-escalation group had 5% nausea and 10% vomiting rates. The estimated mean treatment difference from PBO at Day 85 ranged from 6.3% to -11.3% (Fig 1). Conclusion: This 12-week trial demonstrated substantial weight loss with titration-free weekly dosing. Additionally, the two-step escalation arm was exceptionally well tolerated. Disclosure: R. Stoekenbroek: Employee; Metsera. J. Bisch: None. S. Kolluri: Employee; Metsera. M.A. Noor: Employee; Metsera, Olatec. J. Mallory: Employee; Metsera, Kriya Therapeutics. R. Cunningham: Employee; Metsera. B. Hubbard: Employee; Metsera. S.P. Marso: Employee; Metsera. Stock/Shareholder; Metsera.