Nature communicationsJun 22, 2026

HRS-7535, an oral drug activating the GLP-1 receptor, tested in Chinese adults with obesity but no diabetes in a controlled clinical trial

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 23, 2026

Abstract

At Week 26, participants taking 180 mg of HRS-7535 experienced a 9.36% reduction in body weight compared to placebo.

Oral HRS-7535 demonstrated weight-loss potential in adults with obesity without diabetes.
Participants receiving 60 mg or higher doses showed clinically meaningful weight loss compared to placebo.
Gastrointestinal adverse events were the most common side effects, primarily mild to moderate in severity.
Adverse events occurred more frequently during the escalation of the HRS-7535 dose.
The study involved 235 participants randomized across multiple centers in China.

Simplified

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 (n = 48), 60 mg (n = 47), 120 mg (n = 46), or 180 mg (n = 48), or placebo (n = 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 <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.