The STEP UP and STEP UP T2D clinical trials are the first to investigate whether increasing the dose of semaglutide from the currently approved dose of 2·4 mg to 7·2 mg is safe and leads to additional weight reduction. Trial participants were randomised to receive either the higher 7·2 mg dose of semaglutide, the currently approved 2.4 mg dose, or placebo over 72 weeks. All participants-regardless of treatment group-received lifestyle interventions such as dietary counseling and increased physical activity recommendations.
In adults without diabetes, a 7·2 mg dose of semaglutide led to an average weight loss of nearly 19%, surpassing the 16% loss seen with 2·4 mg and 4% with placebo. Nearly half of the participants on the higher dose lost 20% or more of their body weight, with about one-third losing at least 25%. Participants also experienced improvements in waist circumference, blood pressure, blood sugar, and cholesterol levels, all key factors in reducing obesity-related health risks. Similarly, in adults with obesity and T2D, the 7·2 mg dose resulted in an average 13% weight loss compared to 10% with 2.4 mg and 3.9% with placebo, along with significant reductions in blood sugar levels and waist size.
Both trials reported that the higher dose of semaglutide was safe and generally well tolerated. Gastrointestinal side effects like nausea and diarrhoea, and some sensory symptoms like tingling, were the most common. However, most side effects were manageable, resolved over time, and did not lead to participants dropping out of the trial. No increase in serious adverse events or severe hypoglycaemia was observed with the higher dose.
By delivering greater weight reduction and metabolic benefits while maintaining a favourable safety profile, the authors say this higher dose could help more people reach their health goals and reduce the burden of obesity-related complications worldwide. However, they highlight that further research is needed to fully understand the long-term benefits and risks.
Reference:
Wharton, Sean et al., Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial, The Lancet Diabetes & Endocrinology, DOI: 10.1016/S2213-8587(25)00226-8
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