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Metabolic and Hormonal Factors Underlying endocrine conditions can significantly impair weight loss efforts: Hypothyroidism : Untreated or inadequately managed thyroid dysfunction slows metabolic rate and may blunt Wegovy's effectiveness Polycystic ovary syndrome (PCOS) : Insulin resistance and hormonal imbalances can make weight loss more challenging Cushing's syndrome : Excess cortisol promotes weight gain, particularly central adiposity Sleep disorders : Obstructive sleep apnoea and poor sleep quality disrupt metabolic hormones (leptin, ghrelin) that regulate appetite NICE guidance (CG189) recommends investigating potential secondary causes of obesity when weight loss interventions prove ineffective