Higher dose Semaglutide Shows Critically important Weight Loss in Obesity Trials
New research published in Lancet Diabetes & Endocrinology demonstrates that a higher dose (7.2 mg) of weekly semaglutide can lead to considerable weight loss and improved metabolic health in adults with obesity, including those with type 2 diabetes (T2D). Teh findings suggest this increased dosage could be a valuable treatment option for individuals who haven’t achieved desired results with standard therapies.
Two large, international phase 3 clinical trials – STEP UP and STEP UP T2D – investigated the safety and efficacy of increasing the semaglutide dose from the currently approved 2.4 mg to 7.2 mg. Participants were randomly assigned to receive either the higher dose, the approved dose, or a placebo for 72 weeks, alongside lifestyle recommendations including dietary support and increased physical activity.
The results showed that participants without diabetes experienced an average weight loss of nearly 19% with the 7.2 mg dose, significantly exceeding the 16% reduction seen with 2.4 mg and the 4% reduction observed with the placebo. Almost half of those on the higher dose lost at least 20% of their body weight, and roughly one-third achieved a reduction of 25% or more. Improvements were also noted in waist circumference, blood pressure, blood sugar, and cholesterol levels – all factors linked to obesity-related health risks.
For participants with obesity and T2D, the 7.2 mg dose resulted in a 13% weight loss,compared to 10% with 2.4 mg and 3.9% with the placebo. This was accompanied by significant reductions in blood sugar levels and waist circumference.
Both trials reported the higher dose of semaglutide was safe and generally well-tolerated. The most common side effects were gastrointestinal issues like nausea and diarrhea, and some sensory symptoms such as tingling. These side effects were typically manageable, often resolving over time, and did not lead to a significant number of participants dropping out of the trials. No increase in serious adverse events or severe hypoglycemia was observed with the higher dose.
The study authors conclude that the increased weight loss and metabolic benefits, coupled with a manageable safety profile, suggest this higher dose could help more individuals reach their health goals and lessen the global burden of obesity-related complications. However, they emphasize the need for further research to fully understand the long-term benefits and risks associated with this dosage.
Reference: Wharton, S., Freitas, P., Hjelmesæth, J., Kabisch, M., Kandler, K., Lingvay, I., Quiroga, M., Rosenstock, J., & Garvey, W. T. (2025). Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes & Endocrinology. https://doi.org/10.1016/S2213-8587(25)00226-800226-8)
