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Diabetes and Vascular Disease

SUN-641 - JUV-161 Improves Glucose Metabolism and Muscle Health as Monotherapy and in Combination in Type 2 Diabetic Mice

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Vengadeshprabhu Karuppagounder, Ph.D: No financial relationships to disclose


Background: Skeletal muscle loss and functional decline are underrecognized complications of obesity and type 2 diabetes that worsen insulin resistance and clinical outcomes. Chronic hyperglycemia and impaired insulin signaling disrupt muscle anabolic pathways, yet current therapies do not directly target muscle health. Using a machine learning enabled, multi-omics platform focused on stem cell derived secretomes, Juvena identified JUV-161 as an insulin-sensitizing biologic with muscle protective potential. We evaluated the metabolic and musculoskeletal effects of JUV-161, alone and with semaglutide, in db/db mice, a severe type 2 diabetes model.

Methods: Male db/db (BKS) mice (9 weeks) were randomized into four groups (n=12-15/group): vehicle (HSA), JUV-161 (48mg/kg), semaglutide (6 nmol/kg), or JUV-161 plus semaglutide. Treatments were administered once daily by subcutaneous injection for 21 days. Body weight, body composition (EchoMRI), and fasting blood glucose were monitored weekly. Insulin tolerance testing, glucose stimulation testing, grip strength, and in vivo muscle force (AURORA) were performed during the final week. At study completion, tibialis anterior (TA) and gastrocnemius (GC) weights, serum metabolic parameters, and HbA1C were assessed.

Results: JUV-161 significantly reduced fasting blood glucose over 3 weeks as monotherapy, with further improvement observed in combination with semaglutide. ITT revealed enhanced glucose disposal in JUV-161 treated mice, with the greatest effect in the combination group. Consistent with these findings, serum glucose and HbA1C were reduced compared with vehicle (vehicle 8.3%; JUV-161 7.2%; semaglutide 7.4%; combination 6.3%). Serum chemistry analysis indicated improved liver function with JUV-161 treatment, which was further enhanced by combination therapy. Creatine kinase, creatinine, and glucose were reduced with JUV-161 alone and in combination, whereas triglycerides and VLDL were reduced only with combination therapy. Beyond metabolic improvements, JUV-161 monotherapy and combination treatment significantly enhanced all-limb and forelimb grip strength and improved GC twitch force and force-frequency responses. JUV-161 increased body weight while preserving lean mass overall and as measured specifically in significantly increased TA and GC muscle weights.

Conclusion: JUV-161 improves glycemic control, insulin sensitivity, skeletal muscle mass, and muscle function in a severe model of type 2 diabetes, both alone and in combination with semaglutide. By simultaneously targeting metabolic dysfunction and muscle health, JUV-161 addresses a critical unmet need in diabetes-associated muscle loss and functional decline. These findings support JUV-161 as a promising first-in-class biologic with strong translational potential in type 2 diabetes.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*