Nutrition and Physical Activity in Optimizing Weight Loss and Lean Mass Preservation in the Incretin-Based...

Incretin-based medications have transformed obesity management by enabling substantial body weight reduction. However, the rapid and pronounced loss of body mass necessitates a comprehensive, multidisciplinary approach incorporating nutritional and physical activity strategies to preserve lean mass, optimize functional outcomes, and prevent long-term complications. This narrative review provides a critical overview of this emerging clinical concern, which is expected to gain increasing relevance in the coming years.

A literature review was conducted up to 31 October 2025, focusing on studies addressing nutritional, physical activity, and adjunctive interventions in adults with obesity treated with incretin-based medications.

Incretin-based agents induce significant weight loss, comparable to bariatric surgery, predominantly targeting adipose tissue. Nevertheless, these medications also cause rapid reductions in muscle and bone mass, often accompanied by nutrient deficiencies, which may compromise metabolic health and physical function. Tailored nutritional strategies-including hypocaloric diets enriched in protein and fiber, as well as amino acid, vitamin, and mineral supplementation-are critical to preserve lean mass and support sustained weight maintenance. Concurrently, structured, supervised physical activity, encompassing aerobics, resistance, and strength training, mitigates muscle loss and enhances functional capacity. Emerging pharmacological agents designed to promote adipose tissue reduction while preserving lean mass, as well as interventions targeting gut microbiota modulation, may represent promising adjunctive strategies to optimize long-term outcomes further.

While incretin-based medications produce substantial weight loss, their impact on lean mass underscores the necessity of integrating personalized nutrition, supplementation, and structured exercise to preserve muscle, prevent malnutrition, and optimize long-term health and obesity outcomes.