PURPOSE OF REVIEW: This review explores the integration of semaglutide, a highly effective glucagon-like peptide-1 receptor agonist (GLP-1RA), with medical nutritional therapy (MNT) for the comprehensive management of obesity. Semaglutide promotes significant weight loss and metabolic improvement, but optimal outcomes often require combining this pharmacological treatment with tailored nutritional interventions. This review focuses on two prominent dietary strategies whose nutritional profiles may complement semaglutide's mechanisms of action: the Mediterranean diet (MD) and very-low-energy ketogenic therapy (VLEKT).
RECENT FINDINGS: The MD emphasises balanced macronutrients and anti-inflammatory components, making it particularly suitable for individuals with uncomplicated obesity; it supports gradual and sustainable weight loss while mitigating inflammation and gastrointestinal side effects. Conversely, VLEKT, which induces nutritional ketosis, may be more appropriate for patients with significant cardiometabolic comorbidities, offering rapid and substantial fat mass reduction and improved glycaemic control. Both dietary approaches, when integrated with semaglutide therapy, have the potential to preserve lean body mass, reduce gastrointestinal adverse events, and enhance adherence through improved satiety and tolerability. The proposed integrated approach underscores the importance of personalised nutritional strategies guided by patient-specific metabolic, hormonal, and microbiota profiles, and calls for effective multidisciplinary collaboration among nutritionists, endocrinologists, and behavioural health professionals to optimise therapeutic outcomes. Ultimately, we emphasise that shifting the clinical focus from weight reduction alone to a targeted approach integrating semaglutide with evidence-based nutritional strategies may represent the most promising pathway towards sustainable obesity management.