1652-P: The Effectiveness of Semaglutide on Glucose Tolerance and Body Composition in Obese Diabetic Rhesus Monkeys

Introduction & Objective: This study aimed to investigate the changes of obesity severity, glucose metabolism, and body composition in obese and diabetic rhesus monkeys treated with semaglutide. Methods: We enrolled 12 rhesus monkeys aged between 12-20 years with fasting plasma glucose (FPG) > 5.5 mmol/L, body weight (BW) ranging from 12-20 kg, and fat mass proportion between 20-55%, and randomly assigned them to 4 weeks of treatment with once-weekly subcutaneous semaglutide or placebo, followed by an 8-week washout period. The BW, waist circumference (WC), and metabolic parameters were examined. Body composition was measured using DEXA and MRI monthly. Proportions of total fat body mass (TFM) and total lean body mass (TLM) were shown relative to total body mass. Results: At week 4, in semaglutide group, the changes in BW and WC from baseline were -14.82±2.73% and -12.4±9.3% (vs. placebo, P<0.001). This resulted in reductions from baseline in TFM (-24.08±14.21%, vs. 2.35±9.12% placebo; P=0.0025). TLM decreased from baseline (-7.32±3.37% vs. -0.12±5.99% placebo; P=0.0197); however, there was an increase from baseline in the muscle-to-weight ratio (13.15±7.03% vs. -1.24±5.35 placebo; P=0.0018) and the muscle-to-fat ratio (32.07±15.95% vs. -4.35±14.91% placebo; P=0.0014). Significant declines in FPG (-21.86±7.56% vs. 1.83±4.16% placebo, P=0.0000) and HOMA-IR (-62.46±18.11% vs. -10.58±39.49% placebo; P=0.0026) were noted compared to baseline. Conclusion: These results suggest that semaglutide effectively improves glucose tolerance, reduces BW while increases proportion of TLM in obese T2DM rhesus monkeys. This nonhuman primate model showed similar response to GLP-1 receptor agonist in humans. Z. Yang: None. L. Gong: None. Y. Liang: None. Z. Yao: None. L. Zeng: None. M. Wu: None. Z. Yang: None. W. Zeng: None.