GLP-1/GIP Dual Agonist HRS9531 Shows Promising Phase 2 Data for Obesity Management
More than half of study participants receiving the dual incretin agonist had weight loss of 20% or greater, with no evidence of a plateau and only mild AEs.
Jiangsu Hengrui Pharmaceuticals and Kailera Therapeutics have announced compelling topline results from the phase 2 trial (HRS9531-203) evaluating the efficacy and safety of HRS9531, a novel dual glucagon-like peptide-1 (GLP-1)/gastric inhibitory polypeptide (GIP) agonist, in individuals with overweight or obesity. The findings, released on January 13, 2025, underscore the drug’s potential as a next-generation treatment for obesity and related conditions, the company stated in a news release.1
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The multicenter randomized trial demonstrated that participants with overweight or obesity and without type 2 diabetes who received once-weekly 8-mg subcutaneous injections of HRS9531 achieved a mean weight loss of 22.8%, corresponding to a placebo-adjusted mean weight reduction of 21.1% (P <.001) over 36 weeks. Notably, 59% of participants treated with HRS9531 experienced a weight loss of 20% or greater from their baseline weight, with no evidence of a plateau, according to the statement.
HRS9531 exhibited a favorable safety profile, with most adverse events (AEs) being mild and consistent with other drugs in the GLP-1/GIP receptor agonist class. The most common AEs were gastrointestinal-related and occurred primarily during dose titration.
“These results solidify HRS9531 as a potential breakthrough in chronic weight management,” Ron Renaud, president and CEO of Kailera Therapeutics, said in the press statement. “The 8 mg dose has shown exceptional efficacy and safety, and we are building the infrastructure to advance this promising candidate into a global phase 3 program.”
Previous phase 2 data. The latest findings build on prior results from the HRS9531-201 phase 2 trial, presented in June 2024 at the American Diabetes Association (ADA) Scientific Sessions.2 Participants were randomly assigned to receive once-weekly subcutaneous injections of HRS9531 or a placebo injection across 4 dose cohorts (1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg) for 24 weeks. In this study, participants achieved a maximum placebo-adjusted mean weight loss of 16.7% (P <.001) at the 6-mg dose at 24 weeks. Importantly, both Phase 2 trials utilized a titration protocol that included 12 weeks at the target dose, underscoring the role of gradual dose escalation in optimizing outcomes.2
HRS9531-203. The HRS9531-203 trial, conducted in China, was a multicenter, randomized, double-blind, placebo-controlled phase 2 study. The study enrolled 61 adults, aged 18-65 years, with overweight or obesity (BMI 24–40 kg/m²) but without type 2 diabetes. Participants were randomized 4:1 to receive either HRS9531 or placebo, with a titration schedule leading to the 8-mg target dose over 24 weeks, followed by 12 weeks of maintenance. The primary endpoint was the percentage change in body weight from baseline at 36 weeks. Of the 61 participants, 49 received the investigational medication. The prospects for the dual incretin agonist seem favorable given the high proportion of participants who achieved clinically meaningful weight loss.
The dual GLP-1/GIP receptor agonist has shown efficacy across clinical trials that have enrolled and treated more than 650 participants to date. By targeting both GLP-1 and GIP receptors, HRS9531 leverages complementary pathways to regulate appetite and energy balance, making it a potentially powerful option for chronic weight management.
In addition to ongoing phase 3 trials for obesity and type 2 diabetes in China, Kailera Therapeutics is advancing HRS9531 globally under the name KAI-9531.
Hengrui and Kailera plan to present detailed phase 2 results at an upcoming scientific conference and proceed with global phase 3 studies.
