<p>Bofanglutide is a novel biweekly (once every two weeks; Q2W) glucagon-like peptide-1 receptor agonist. We evaluated the efficacy and safety of bofanglutide in Chinese adults with overweight or obesity in a randomized, double-blind, placebo-controlled phase 2b trial (ClinicalTrials.gov, NCT06256562). Adults with overweight (body mass index [BMI] ≥24, &lt;28 kg/m²) and at least one weight-related comorbidity, or obesity (BMI ≥ 28 kg/m²), were randomly assigned to five dose groups: 12 mg Q2W, 18 mg Q2W, 24 mg Q2W, 48 mg Q2W, and 24 mg once weekly (QW), with randomization to bofanglutide or placebo within each dose group. The primary endpoint was the percentage change in body weight from baseline to week 30. Between June 8, 2023, and June 5, 2024, 340 participants (185 [54.4%] male; mean age, 33.1 years; mean body weight, 95.6 kg; mean BMI, 33.2 kg/m²) were randomized into the following groups: bofanglutide 12 mg Q2W (<i>n</i> = 52), 18 mg Q2W (<i>n</i> = 53), 24 mg Q2W (<i>n</i> = 52), 48 mg Q2W (<i>n</i> = 64), 24 mg QW (<i>n</i> = 53), or placebo (<i>n</i> = 66). Overall, 286 participants (84.1%) completed the trial. The mean percentage change in body weight from baseline to week 30 ranged from −9.75% to −16.69% with bofanglutide, compared with −1.15% with placebo (all <i>p</i> &lt; 0.001 versus placebo). Adverse events occurred in 98.9% (271/274) of the bofanglutide group versus 86.4% (57/66) of the placebo group and were mostly grade 1–2 gastrointestinal events (83.9% [230/274] with bofanglutide and 33.3% [22/66] with placebo). Bofanglutide is generally well tolerated and has a robust ability to reduce body weight.</p>