The Integration of Lifestyle Modification Advice and Diet and Physical Exercise Interventions: Cornerstones in the Management of Obesity with Incretin Mimetics

Background: The introduction of incretin mimetics (IMs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as liraglutide and semaglutide, as well as dual GLP-1/glucose-dependent insulinotropic polypeptide receptor co-agonists (GLP-1/GIP RAs) like tirzepatide, has revolutionized obesity treatment. These obesity management medications promote significant weight loss with metabolic and cardiovascular improvements. However, pharmacotherapy alone seems insufficient to address the multifactorial nature of obesity. While IMs suppress appetite and reduce caloric intake, they do not prevent potential nutrient deficiencies and possible loss of skeletal muscle mass, nor do they guarantee lasting behavioral changes necessary for long-term weight management, particularly in the absence of other complementary interventions. Summary: In this context, a clear distinction must be made between general lifestyle modification advice (Ls-M) and personalized and structured dietetic and physical exercise interventions (D-PE-Is). Ls-M, including a balanced diet and regular physical activity, is essential for preventing obesity and reducing the risk of weight gain and associated metabolic disorders. However, once obesity is established, D-PE-I becomes necessary. Unlike Ls-M, D-PE-I integrates personalized nutritional strategies with structured exercise to maximize fat loss, preserve skeletal muscle mass and function, and enhance metabolic health. This narrative and concept-driven review aimed to delineate key areas for future clinical trials and meta-analyses. Key Messages: IMs have brought important progress in the management of obesity, contributing meaningfully to current therapeutic approaches. However, pharmacotherapy alone is not sufficient to ensure long-term success. While lifestyle advice may aid in prevention, structured and personalized dietetic and physical exercise interventions are essential once obesity is established. Their integration with IMs is crucial to support long-term weight maintenance and improve overall health and quality of life.