2584-P: Durable and Exposure-Dependent Antiobesity Efficacy of IVL3021, a Once-Monthly Long-Acting Semaglutide in a Rat Diet-Induced Obesity Model

Introduction and Objective: Long-acting injectable (LAI) GLP-1 receptor agonists aim to improve treatment adherence and durability by maintaining sustained drug exposure. However, conventional weekly dosing is often associated with fluctuating plasma concentrations and rapid body weight (BW) regain after treatment discontinuation. This study evaluated the non-clinical anti-obesity efficacy of IVL3021, a one-month LAI formulation of semaglutide developed using IVL-DrugFluidics® technology, in a rat diet-induced obesity (DIO) model. Methods: IVL3021 was administered subcutaneously to DIO rats as single or repeated doses. BW changes were assessed in relation to plasma drug concentrations. Comparative studies versus Wegovy®, treatment discontinuation, and switch-regimen (Wegovy to IVL3021) evaluations were conducted. Plasma triglycerides (TG), liver enzymes (AST and ALT), and body composition by dual-energy X-ray absorptiometry (DEXA) were analyzed. Results: IVL3021 induced a marked, plasma concentration-dependent reduction in BW. Repeated dosing of IVL3021 resulted in controlled accumulation of systemic exposure and enhanced BW reduction, enabling the low-dose group to achieve BW reduction comparable to Wegovy. Following treatment cessation, Wegovy-treated animals exhibited rapid BW regain, whereas a single administration of IVL3021 sustained BW reduction for up to 8 weeks. BW reduction was maintained in the Wegovy-to-IVL3021 switch regimen. In addition, IVL3021 significantly reduced plasma TG levels and AST/ALT compared with controls. DEXA analysis demonstrated a statistically significant reduction in body fat mass in IVL3021-treated groups. Conclusion: IVL3021 demonstrated robust and durable anti-obesity efficacy with favorable metabolic improvements in a rat DIO model. These findings support IVL3021 as a promising long-acting GLP-1 receptor agonist formulation for sustained weight management.