126-OR: Efficacy and Safety of a Novel Dual GLP-1/GIP Receptor Agonist in Participants with Type 2 Diabetes Mellitus Up to 32 Weeks

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Introduction and Objective: HRS9531, a novel once-weekly (QW) dual GLP-1/GIP receptor agonist, showed preliminary efficacy with good tolerability in T2DM participants. This phase 2 study further evaluated the efficacy and safety of HRS9531 in Chinese T2DM participants with treatment to 32 weeks which consisted of a 20-week (W) core treatment followed by a 12W extension treatment.Methods: In this randomized, double-blind phase 2 trial, participants with T2DM, HbA1c 7.5%-10.5%, inadequately controlled with lifestyle or stable metformin, were randomized to receive QW subcutaneous HRS9531 (1, 2, 3 and 4.5 mg) and corresponding placebo. During extension, HRS9531 doses remained unchanged while participants in placebo group were added HRS9531 1 mg QW (placebo-HRS9531 1 mg/W group). Primary endpoint was change from baseline in HbA1c at 20W. The efficacy and safety in 32W were also observed.Results: Of 199 randomized participants, 186 received and 180 completed the extension treatment. At 20W, mean HbA1c changes from baseline were from -2.1% to -2.7% in HRS9531 groups. HRS9531 maintained efficacy over 32 weeks. Mean changes in HbA1c were -2.1%, -2.5%, -2.7% and -2.4% in the 1, 2, 3 and 4.5 mg groups, respectively, with 91.7% of participants in the 4.5 mg group achieving HbA1c < 7.0%. The change in HbA1c of the placebo-HRS9531 1 mg/W group was -2.0%. HRS9531 induced a continuous dose-dependent body weight loss ranging from -4.0% to -8.9%. At 32W, HRS9531 was associated with improvement in systolic blood pressure, TG levels and UACR up to -9.5 mmHg, -25.7% and -61.8%, respectively. Most emergent-treatment adverse events (TEAEs) were mild or moderate. The most common TEAEs were diarrhea, decreased appetite and nausea. No clinically significant hypoglycemia or severe hypoglycemia was reported.Conclusion: HRS9531 demonstrated improved and sustained glycemic control and weight loss over 32 weeks treatment, with a favorable safety and low risk of hypoglycemia.

Disclosure

J. Zhao: None. M. Zhao: None. W. Song: None. D. Wang: None. X. Zhang: None. Y. Hui: None. Y. Zhou: None. Y. Lu: None. M. Zhang: None. C. Jiang: None. F. Lv: None. L. Zhang: None. M. Zeng: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. L. Zhang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Cui: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. J. Wang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd.



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