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consideration of dose escalation 6 months : Formal assessment of treatment efficacy according to appropriate criteria: For diabetes (NICE NG28): HbA1c reduction of at least 11 mmol/mol (1.0%) and weight loss of at least 3% For weight management: At least 5% weight loss from baseline on maintenance dose (per SmPC and NICE guidance) Annually thereafter : Ongoing monitoring of metabolic parameters, cardiovascular risk factors, and treatment appropriateness Treatment adjustments may be necessary if: Side effects remain intolerable despite supportive measures Weight loss plateaus before reaching target (may warrant dose increase if not at maximum) Inadequate glycaemic control persists (may require additional diabetes medications) Significant weight loss goals are achieved (maintenance strategies and potential dose reduction) Patients should maintain open communication with their healthcare team, reporting both positive developments and concerns

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We therefore investigated the predictive value of these variables in our cohort, after adjusting for the non-genetic factors described above (Supplementary Information)

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