Novel HRS9531 shows promise as treatment for obesity in Chinese adults

Once-weekly treatment with HRS9531, a novel dual GLP-1* and GIP** receptor agonist, resulted in substantial reductions in body weight among Chinese patients with obesity, according to a study presented at ADA 2024.

“People living with obesity are at high risk of developing chronic diseases such as type 2 diabetes and cardiovascular disease. Losing weight significantly reduces the risk of those diseases,” said Prof Xiaoying Li from the Department of Endocrinology and Metabolism at Zhongshan Hospital Fudan University in China in a press release.

“Since dietary and exercise intervention alone is often not enough, we were pleased to see that this could be a potentially promising treatment for weight management, potentially enhancing their overall health and significantly reducing the societal burden of obesity,” she noted.

The phase II, double-blind, placebo-controlled trial analysed 249 Chinese adults who were overweight or obese (BMI 28–40 kg/m²) but without diabetes. Participants were randomly assigned to receive once-weekly subcutaneous injections of HRS9531 (1, 3, 4.5, or 6 mg) or placebo for 24 weeks.

By week 24, patients who received HRS9531 achieved significant body weight reductions of 5.8 percent, 13.4 percent, 14 percent, and 16.8 percent in the 1-, 3-, 4.5-, and 6-mg groups, respectively, (p<0.0001 for all). However, those who received placebo only achieved a 0.1-percent weight reduction. [ADA 2024, abstract 1861-LB]

In addition, more patients in the HRS9531 groups achieved ≥5-percent reduction in body weight (52 percent [1 mg], 88.2 percent [3 mg], 92 percent [4.5 mg], and 91.8 percent [6 mg]) than those in the placebo group (10.2 percent).

As a result, mean changes in waist circumference in the HRS9531 groups ranged from -5.14 to -12.73 cm compared with -1.82 cm with placebo.

Patients who received HRS9531 also had a greater reduction in mean systolic blood pressure from baseline to week 42 than those who received placebo (ranging from -4.46 to -8.33 vs -0.41 mm Hg).

In terms of safety, the most common adverse events (AEs) were nausea, diarrhoea, decreased appetite, and vomiting, which occurred mainly during dose escalation. All AEs were mild or moderate in severity.

There were no serious AEs or drug discontinuations related to the study drug reported.

“Overall, HRS9531 outperformed placebo [in effectively reducing body weight and blood pressure], with a favourable safety profile,” said the researchers.

“These data support further clinical development of HRS9531 for obesity treatment,” they added.

Furthermore, a phase III study of HRS9531 is already underway in Chinese overweight or obese individuals, and multiregional studies are being planned, the researchers mentioned in a press release.