Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Type 1 diabetes mellitus (T1DM) represents a complex clinical challenge for health systems. The autoimmune destruction of pancreatic beta cells leads to a complete lack of insulin production, exposing people to a lifelong risk of acute (DKA, coma) and chronic complications (macro and microvascular). Physical activity (PA) has widely demonstrated its efficacy in helping diabetes treatment. Nutritional management of people living with T1DM is particularly difficult. Balancing macronutrients, their effects on glycemic control, and insulin treatment represents a complex clinical challenge for the diabetologist. The effects of PA on glycemic control are largely unpredictable depending on many individual factors, such as intensity, nutrient co-ingestion, and many others. Due to this clinical complexity, we have reviewed the actual scientific literature in depth to help diabetologists, sport medicine doctors, nutritionists, and all the health figures involved in diabetes care to ameliorate both glycemic control and the nutritional status of T1DM people engaging in PA. Two electronic databases (PubMed and Scopus) were searched from their inception to January 2024. The main recommendations for carbohydrate and protein ingestion before, during, and immediately after PA are explained. Glycemic management during such activity is widely reviewed. Micronutrient needs and nutritional supplement effects are also highlighted in this paper.