AimsTo determine the relationship between exposure and weight‐loss trajectories for the glucagon‐like peptide‐1 analogue semaglutide for weight management.Materials and MethodsData from one 52‐week, phase 2, dose‐ranging trial (once‐daily subcutaneous semaglutide 0.05–0.4 mg) and two 68‐week phase 3 trials (once‐weekly subcutaneous semaglutide 2.4 mg) for weight management in people with overweight or obesity with or without type 2 diabetes were used to develop a population pharmacokinetic (PK) model describing semaglutide exposure. An exposure‐response model describing weight change was then developed using baseline demographics, glycated haemoglobin and PK data during treatment. The ability of the exposure‐response model to predict 1‐year weight loss based on weight data collected at baseline and after up to 28 weeks of treatment, was assessed using three independent phase 3 trials.ResultsBased on population PK, exposure levels over time consistently explained the weight‐loss trajectories across trials and dosing regimens. The exposure‐response model had high precision and limited bias for predicting body weight loss at 1 year in independent datasets, with increased precision when data from later time points were included in the prediction.ConclusionAn exposure‐response model has been established that quantitatively describes the relationship between systemic semaglutide exposure and weight loss and predicts weight‐loss trajectories for people with overweight or obesity who are receiving semaglutide doses up to 2.4 mg once weekly.

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