1635-P: Survodutide Weight Loss Is Associated with Changes in Food Preference and Improvement of Dyslipidemia in the Free Choice Diet–Induced Obese Hamster Model

Introduction & Objective: Survodutide, a glucagon/GLP-1 receptor dual agonist, has recently shown significant weight loss in a Phase II trial. To test whether this weight loss is associated with changes in food preference and improvement in dyslipidemia, we evaluated survodutide in the free choice diet-induced obese and dyslipidemic hamster model, with human-like lipoprotein metabolism.

Methods: Obesity and dyslipidemia were induced with a 20-week free choice diet, with a choice between control chow or high fat/cholesterol diet, and normal or 10% fructose water. Obese hamsters were kept on this free choice diet and treated subcutaneously, once daily for 2 weeks with vehicle or survodutide 20 nmol/kg.

Results: Survodutide treatment for 2 weeks led to a 19% body weight reduction (p<0.0001 vs vehicle). Compared to vehicle, both normal water and chow diet intake were significantly lower during week 1 of survodutide treatment, then returned to baseline values. In contrast, both 10% fructose water and high fat/cholesterol diet intake were rapidly reduced during the whole treatment period (p<0.0001). Survodutide significantly reduced fasting glycemia and hyperinsulinemia, leading to a 75% reduction in HOMA-IR index (p<0.0001). Survodutide reduced plasma free fatty acids (-49%) and triglycerides (-75%; both p<0.001 vs vehicle). Survodutide reduced plasma total cholesterol levels (-41%, p<0.001), resulting in cholesterol lowering in all lipoprotein fractions, including LDL-cholesterol (-31%, p<0.0001 vs vehicle). These effects were further confirmed with fast protein liquid chromatography lipoprotein profiles.

Conclusion: Survodutide induces weight loss in the free choice diet-induced obese hamster model through beneficial changes in food preference, leading to improvement in HOMA-IR and dyslipidemia. These data highlight the potential benefits of survodutide for the treatment of obesity and related comorbidities.