Optimizing Adherence and Outcomes: Potential Strategies to Enhance the Effectiveness of nutrient-stimulated hormone therapies

Nutrient-stimulated hormone therapies (NuSH) therapies, a key class within obesity management medications, have reshaped obesity and type 2 diabetes care, producing substantial weight loss, improved glycaemic control, and significant cardiometabolic benefits in adults and adolescents. Yet outcomes vary widely, and NuSH therapy-induced changes in appetite, eating behaviour, and gastrointestinal function can compromise nutrient intake, lean mass preservation, and long-term adherence. This review synthesises evidence across nutrition, behavioural science, microbiota research, and metabolic-bariatric surgery (MBS) to outline supportive strategies that optimise clinical outcomes with NuSHs.Preclinical studies consistently show that NuSH therapies shift gut microbiota toward "lean-associated" profiles, while emerging human findings suggest that baseline microbial signatures may contribute to variability in response and tolerability. However, evidence in humans remains limited, heterogeneous, and underpowered. Across age groups, structured nutritional and behavioural support remains essential to ensure nutrient adequacy, manage side effects, strengthen adherence, and guide sustainable lifestyle change.Key research priorities include defining behavioural and microbial contributors of treatment response and adherence, evaluating microbiota-targeted adjuncts, and developing scalable, multidisciplinary care models for both adult and paediatric populations. NuSH therapies are powerful tools, but their long-term success depends on integrated, personalised nutrition and behavioural care, with growing opportunity for microbiome-informed approaches.