Metsera, Inc. announced positive topline results from its Phase 2a clinical trial of MET-097i, a potential once-monthly, ultra-long acting GLP-1 receptor agonist, on January 7, 2025. The trial demonstrated significant weight loss and a favorable tolerability profile in overweight and obese participants without type 2 diabetes.
The randomized, double-blind, placebo-controlled trial involved 120 participants divided into five cohorts. Four cohorts received fixed weekly doses of MET-097i (0.6mg, 0.8mg, 1.0mg, or 1.2mg) for 12 weeks, while the fifth cohort received escalated doses (0.4mg, 0.8mg, and 1.2mg) over the same period. At week 13, participants received a two- or four-fold dose increase to assess tolerability for potential monthly dosing.
Significant Weight Loss Achieved
Weight loss was dose-dependent, with the 1.2mg cohort experiencing a mean body weight reduction of 11.3% (placebo-adjusted). Some individuals in this group achieved ~20% weight loss after 12 weeks. Notably, a weight loss plateau was not observed, suggesting potential for further weight reduction with longer-term dosing. All cohorts achieved clinically meaningful and statistically significant weight loss after 12 weeks.
Favorable Tolerability Profile
MET-097i was generally well-tolerated across all dose groups, with predominantly mild and short-lived gastrointestinal adverse events. The dose-escalated cohort showed particularly compelling tolerability, with only one case of mild nausea and two cases of mild vomiting observed among 20 participants. This cohort also experienced a mean body weight loss of 6.3% (placebo-adjusted).
Potential for Monthly Dosing
Pharmacological exposure to MET-097i increased approximately four-fold over 12 weeks in the fixed-dose cohorts, driven by the drug's 15-16 day half-life. The step-up to a four-fold higher dose at week 13 was well-tolerated, supporting the feasibility of monthly dosing. Metsera plans to initiate an additional study in early 2025 to confirm these findings across multiple monthly doses.
Expert Commentary
John Buse, M.D., Director of the UNC Diabetes Center at University of North Carolina School of Medicine, stated, "Taken together, these data suggest that MET-097i has the potential to be a foundational therapy for people with obesity and overweight, by virtue of its effectiveness, compelling tolerability profile and flexible options for dosing, including titration-free weekly dosing and monthly dosing."
Steve Marso, M.D., Chief Medical Officer of Metsera, added, "These data strengthen our view of MET-097i as the potential first ultra-long acting GLP-1RA. The powerful reductions in weight affirm our earlier studies. We are also excited by the emerging tolerability and dosing profile of MET-097i, which may offer versatility and meaningful advantages for patients."
Ongoing and Future Studies
Metsera's Phase 2b trial of MET-097i in individuals with obesity or overweight is fully enrolled with 239 participants, with topline data expected in mid-2025. Additional trials exploring MET-097i in obesity, overweight, and type 2 diabetes, including monthly dosing regimens, are planned for 2025. Successful completion of these trials will pave the way for Phase 3 trials.
