GZR18, a GLP-1 analog with once-weekly or bi-weekly dosing for body weight management: A randomized, placebo-controlled, phase 1b/2a trial.

GZR18 is a glucagon-like peptide-1 receptor agonist under development for overweight/obesity. In this randomized, placebo-controlled phase 1b/2a trial in Chinese adults with overweight or obesity, different dose titration regimens and dosing frequencies (once-weekly [QW] vs. bi-weekly [Q2W]) are evaluated to assess safety and weight-loss efficacy over 26 weeks (Part A) or 35 weeks (Part B). Sixty participants are enrolled, of whom 46 complete the trial. The least-squares mean change in body weight is -9.36% for GZR18 vs. 6.68% for placebo in Part A and -17.8% (QW) and -12.8% (Q2W) for GZR18 vs. 0.7% for placebo in Part B; GZR18 also improves other weight-related and metabolic parameters. GZR18 is generally safe and well tolerated, with mostly mild-to-moderate gastrointestinal adverse events and no investigational-product-related serious adverse events reported. These findings warrant larger and longer trials of GZR18 for body weight management. The trial is registered at ClinicalTrials.gov (NCT06256536).