Introduction: Abnormal post-prandial satiety obesity phenotype (APS+) is characterized by rapid gastric emptying. The GLP-1 analog liraglutide delays gastric emptying and in adults with APS+, its use is associated with greater weight loss compared to individuals without APS (APS-). A machine-learning gene risk score (ML-GRS) biomarker has been shown to predict APS and the response to liraglutide with accuracy. Our aim is to determine the applicability of this ML-GRS to predict weight loss response to semaglutide and tirzepatide.
Methods: From a Mayo Clinic multi-center biobank and outcomes registry of adults with obesity undergoing weight loss interventions, we selected those taking semaglutide or tirzepatide. Using saliva or blood samples, we generated an ML-GRS to determine APS phenotype (“APS+” or “APS-”). Endpoints: total body weight loss (TBWL) % at 3, 6, and 12 months by APS status, percentage of adults achieving ≥5, 10, 15, and 20% TBWL at 12 months by APS status; and the probability of the ML-GRS to predict ≥5% of TBWL after 12 months of semaglutide and/or tirzepatide.
Results: We included 137 adults: 91 APS+ and 46 APS-. There were no significant differences in age, race, weight, BMI, medication used and dosage achieved, or co-morbidities among the two groups. Compared to APS-, APS+ had superior TBWL% at 12 months (-13 ± 10% vs -19 ± 10%, n=57, p=0.01) but not at 3 or 6 months. The percentage of adults achieving ≥5, 10, and 20% TBWL at 12 months was significantly greater in APS+. When analyzed by medication, differences in TBWL% and categorical TBWL outcomes among the two groups were replicated with semaglutide but not with tirzepatide. The AUC of the ML-GRS to predict ≥5% of TBWL after 12 months of semaglutide was 0.7 (95% CI [0.5-0.9], p=0.06).
Conclusion: An APS+ ML-GRS is associated with greater weight loss response to semaglutide but not tirzepatide at 12 months. Larger and more diverse studies are needed to better assess the accuracy of this biomarker.
E. Tama: None. S. Fansa: None. D. Anazco: None. R. Rivera: None. W. Ghusn: None. L. Cifuentes: None. A. Acosta: Consultant; Amgen Inc., Regeneron Pharmaceuticals Inc., Nestlé Health Science, Structure Therapeutics, Inc., Boehringer-Ingelheim. Research Support; Vivus. Consultant; Currax. Other Relationship; Gila Therapeutics, Phenomix Sciences. Speaker's Bureau; Eli Lilly and Company. M.D. Hurtado: None.
