Precision Obesity Medicine: Genetic Prediction of Response to GLP-1/GIP Agonists.

Obesity is a chronic multifactorial disease with a strong genetic component. Although glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, such as tirzepatide, are highly effective treatments for obesity, substantial inter-individual variability in weight loss response remains. Genetic factors may contribute to these differences in treatment outcomes. The aim of this prospective cohort study is to investigate whether a Genetic Risk Score (GRS) and selected obesity-related single nucleotide polymorphisms (SNPs) can predict weight loss response to semaglutide or tirzepatide in adults with obesity. Participants initiating treatment with either medication will undergo clinical, biochemical, and genetic assessment at baseline and will be followed for six months. The study will evaluate the association between genetic markers and treatment response and develop predictive models integrating genetic and clinical variables. The findings may contribute to the development of personalized treatment strategies for obesity.

Inclusion Criteria: * Age ≥18 years * BMI ≥40 kg/m² or ≥37 kg/m² with comorbidities * Initiation of semaglutide or tirzepatide Exclusion Criteria: * Prior bariatric surgery * Secondary causes of obesity * Active malignancy * Chronic pancreatitis * Family history of medullary thyroid carcinoma