Nutritional Challenges of Incretin-Based Obesity Management Medications: Implications for Clinical Practice

Several novel incretin-based obesity management medications (OMMs) have recently been approved for chronic weight management in adults with obesity or overweight. These agents have demonstrated substantial weight reduction effects alongside glucoregulatory and cardioprotective benefits. However, the use of incretin-based OMMs presents nutritional challenges that remain insufficiently addressed. These include side effects such as gastrointestinal disturbances and loss of lean body mass, which may compromise nutritional status, reduce energy expenditure, and heighten risk of rebound weight gain, sarcopenia, and frailty. Moreover, although these medications effectively suppress energy intake and reduce food quantity, they may also have unintended effects on diet quality, potentially influencing macronutrient distribution, ultraprocessed food consumption, risk of vitamin and mineral deficiencies, and disordered eating behaviors, which could undermine long-term weight maintenance and the cardiometabolic benefits achieved through these pharmacotherapy agents. Emerging evidence suggests that specific dietary and behavioral strategies, such as higher protein intake, resistance training, nutrient-dense eating patterns, and fostering adaptive eating behaviors, may help mitigate nutritional challenges and physiologic deterioration during significant weight reduction while also supporting cardiometabolic health maintenance. However, the application of these strategies as adjunct treatments alongside the new OMMs remains unclear. This narrative review summarizes the current literature on these issues and proposes dietary interventions and behavioral modification strategies aimed at mitigating the adverse effects that can be associated with incretin-based OMMs. These considerations are increasingly important given the expanding use of these medications, the degree of weight reduction they induce, and the implications for specific at-risk groups, including aging populations prone to muscle and functional decline and individuals with pre-existing conditions of nutritional deficiencies, chronic diseases, and disordered eating patterns.