MON-594 JUV-161 Improves Glucose Metabolism and Muscle Health in Type 2 Diabetes Mice

Abstract Disclosure: V. Karuppagounder: None. R. Datta: None. H.J. Kim: None. A. Koranne: None. A. Yang: None. S. Louie: None. H. Song: None. Z. Li: None. T. Mai: None. B. Anand: None. P. Handa: None. J.D. O'Connell: None. H. Yousef: None. Obesity and diabetes are major risk factors for sarcopenia due to several shared underlying conditions. Metabolic dysregulations such as insulin resistance contribute to impaired muscle protein synthesis and muscle breakdown. Therefore, we assessed the impact of long-term treatment with JUV-161, a novel secreted protein that promotes insulin sensitization, on blood glucose and muscle in db/db mice, a model of metabolic dysregulations.Secreted proteins, though historically difficult to screen, represent a promising category of biologics with established therapeutic potential. Juvena’s a biologics-driven drug discovery and development platform combines machine learning with multi-omics, facilitating the identification of potential therapeutic candidates from an exclusive library of stem cell-secreted proteins. Using this platform, JUV-161 was developed as a biologic for treating myopathies, including diabetes related sarcopenia.Chronic administration of JUV-161 (daily SC injection) for 26 days in db/db mice led to a 20% increase in insulin sensitivity (improved insulin resistance) compared to the vehicle (HSA)-treated group (N=22; p<0.001). Furthermore, JUV-161 treatment significantly improved overall lean mass, causing a 4.6% increase in the percentage change of lean mass from baseline. Additionally, JUV-161 treatment significantly reduced serum glucose levels (810.8 mg/dL vs. 665.6 mg/dL in the vehicle-treated group; p<0.001), serum aspartate aminotransferase (AST) levels (250.4 U/L vs. 143.2 U/L in the vehicle-treated group; p<0.05), serum creatine kinase (CK) levels (516.1 U/L vs. 285.4 U/L in the vehicle-treated group; p<0.05), and serum creatinine levels (0.475 mg/dL vs. 0.358 mg/dL in the vehicle-treated group; p<0.0001). HbA1c was also lower with JUV-161 treatment (10.1% vs. 8.2% in the vehicle-treated group). Moreover, JUV-161 treatment for 26 days led to significantly increased tibialis anterior (TA) and gastrocnemius (GC) muscle weights (TA: 0.00135 g/mm compared to 0.00168 g/mm in the vehicle-treated group, p<0.001; GC: 0.00459 g/mm compared to 0.00497 g/mm in the vehicle-treated group, p<0.05), indicating improved muscle gain. Our findings suggest that JUV-161 can improve insulin sensitivity and promote lean muscle mass while protecting against liver and kidney damage in a model of type 2 diabetic myopathy. Treatment with JUV-161 could be a promising approach to manage muscle wasting in people with type 2 diabetes, particularly for preserving muscle mass during weight loss or injury recovery. Presentation: Monday, July 14, 2025