Abstract: FR-OR088
Efficacy and Safety of the Oral Small-Molecule GLP-1 Receptor Agonist HRS-7535 in Patients with Diabetic Kidney Disease
Session Information
- Late-Breaking Research Orals - 2
November 07, 2025 | Location: Grand Ballroom C, Convention Center
Abstract Time: 04:30 PM - 04:42 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Du, Xiaoying, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Lv, Rong, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Ye, Zi, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
- Peng, Liang, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
- Xu, Yimei, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
- Lin, Xiang, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
- Li, Lu, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
Background
Evidence supporting the renal benefits of oral small-molecule GLP-1 receptor agonists (GLP-1RAs) in diabetic kidney disease (DKD) is limited. In patients receiving standard of care (SOC), including renin–angiotensin system inhibitors (RASi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and finerenone, the potential additive renal protection of GLP-1RAs requires further evaluation.
Methods
In this multicenter, randomized, double-blind, placebo-controlled phase 2 trial (NCT06415214), a total of 281 eligible patients with DKD and a urinary albumin-to-creatinine ratio (UACR) ≥300–<3000 mg/g were randomized (1:1:1) to HRS-7535 30 mg, 90 mg, or placebo for 16 weeks. The efficacy and safety assessments were conducted every 4 weeks.
Results
At baseline, the median UACR was 763.5 mg/g, and 85.7%, 64.6%, and 24.3% of patients were receiving RASi, SGLT2i, and finerenone, respectively. At Week 16, the geometric mean percentage change in UACR from baseline was –30% for HRS-7535 30 mg, –46% for 90 mg, and –14% for placebo, corresponding to placebo-adjusted changes of –19% (P=0.031) and –38% (P<0.0001) for 30 mg and 90 mg, respectively (Fig. 1A). The 90 mg dose led to greater reductions in HbA1c, body weight, blood pressure, liver enzymes, and blood lipids compared with placebo (Fig. 1B). Most adverse events were gastrointestinal-related and mild to moderate in severity (Fig. 1B).
Conclusion
In patients with DKD and persistent macroalbuminuria despite SOC, the oral small-molecule GLP-1RA HRS-7535 significantly reduced albuminuria and improved multiple metabolic parameters, with a safety profile consistent with GLP-1RAs. HRS-7535 may provide a new therapeutic option for patients with DKD.
Figure 1
Funding
- Commercial Support – Jiangsu Hengrui Pharmaceuticals Co., Ltd.