Summary
This paper reports a 52-week off-treatment extension of the STEP 1 randomised controlled trial, examining what happens to body weight and cardiometabolic markers after semaglutide 2.4 mg is discontinued in adults with overweight or obesity. The findings suggest that participants regained a substantial proportion of the weight lost during the treatment phase and that associated cardiometabolic improvements were largely reversed following withdrawal, indicating that the metabolic benefits of semaglutide are contingent on continued treatment. The study contributes important evidence on the chronic nature of obesity and the limitations of time-limited pharmacological intervention without ongoing therapy or lifestyle support.
UK applicability
The findings are directly relevant to UK clinical practice and NHS prescribing policy, particularly given NICE guidance on semaglutide (Wegovy) for weight management; the evidence that benefits are not sustained after cessation has implications for decisions about treatment duration, commissioning, and the support structures needed alongside pharmacotherapy.
Key measures
Body weight (kg and % change); BMI; waist circumference; blood pressure (mmHg); HbA1c (%); fasting plasma glucose (mmol/L); lipid profile (LDL-C, HDL-C, triglycerides); cardiometabolic composite risk markers
Outcomes reported
The study measured body weight trajectory and cardiometabolic risk factors (including blood pressure, lipids, and glycaemic markers) in participants following withdrawal of once-weekly semaglutide 2.4 mg after 68 weeks of treatment. It assessed the extent to which weight and cardiometabolic improvements were maintained or reversed during a 52-week off-treatment follow-up period.
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