<p>HRS-7535 is an orally active small-molecule glucagon-like peptide-1 receptor agonist that showed weight-loss potential in a phase 1 study. In this completed multicenter, randomized, double-blind, placebo-controlled phase 2 trial conducted at 29 centers in China, we evaluated the efficacy and safety of HRS-7535 in adults with obesity without diabetes. 235 participants with a body mass index of 28.0–40.0 kg/m² were randomized a 1:1:1:1:1 ratio to once-daily oral HRS-7535 at target doses of 30 mg (<i>n</i> = 48), 60 mg (<i>n</i> = 47), 120 mg (<i>n</i> = 46), or 180 mg (<i>n</i> = 48), or placebo (<i>n</i> = 46); all randomized participants were included in the analyses. Primary endpoint was percentage change in body weight from baseline to Week 26. At Week 26, least-squares (LS) mean percentage changes in body weight were −2.99% with 30 mg, −7.09% with 60 mg, −6.17% with 120 mg, and −9.36% with 180 mg, versus −2.50% with placebo. Corresponding placebo-adjusted LS mean differences were −0.49%, −4.60%, −3.67%, and −6.87% (P = 0.7104, 0.0006, 0.0062, and &lt;0.0001, respectively). Gastrointestinal adverse events were the most common, were predominantly mild to moderate, and occurred more frequently during dose escalation. Overall, once-daily oral HRS-7535 at doses of 60 mg or higher produced clinically meaningful weight loss and was generally well tolerated.Trial registration: ClinicalTrials.gov identifier NCT06250946</p>