466-P: Therapeutic Efficacy of Monthly Semaglutide-Loaded Microsphere Injections in Zucker Diabetic Fatty Rats

Introduction: This study aimed to develop semaglutide-loaded microsphere monthly injectables using a novel biodegradable microsphere manufacturing technology, and to compare its therapeutic efficacy with both semaglutide solution, administered weekly injectables, and semaglutide microsphere, administered monthly injectables, in male Zucker diabetic fatty (ZDF) rats and ZDF lean control rats. Methods: Semaglutide microsphere was prepared by water-in-oil-in-water (w/o/w) emulsion solvent evaporation method using poly(D, L-lactide-co-glycolide) (PLGA). Therapeutic efficacy was evaluated by measuring blood glucose in both Zucker diabetic fatty (ZDF) and ZDF lean control rats. Subcutaneous administrations were performed once for the Semaglutide microsphere and vehicle control groups, while the Semaglutide solution was administered four times at weekly intervals. Results: The Semaglutide microsphere significantly decreased blood glucose concentration compared to both the vehicle and semaglutide solution groups for four weeks, resembling levels in the lean control group (100 mg/dL) (Figure 1). Conclusion: The Semaglutide microsphere injectables, administered monthly, showed the potential to substantially reduce the frequency of administrations compared to the commercial product, Ozempic® and Wegovy®, thereby potentially enhancing patient compliance. Disclosure J. Park: None. C. Kim: None. T. An: None.