Enhanced Efficacy of High-Dose Semaglutide in Obesity and Type 2 Diabetes: STEP UP Trials Find - Video

A higher weekly dose of semaglutide (7.2 mg) may offer a powerful new treatment for obesity, delivering significantly greater weight loss and health benefits than the currently approved dose, according to two international phase 3 clinical trials published in The Lancet Diabetes & Endocrinology. The STEP UP and STEP UP T2D trials suggest that this increased dosage could be particularly effective for adults with obesity, including those with type 2 diabetes (T2D), who have not achieved sufficient weight reduction with existing therapies.

Semaglutide, a GLP-1 receptor agonist originally developed to manage diabetes, has already demonstrated weight loss benefits at lower doses. These new trials are the first to test whether increasing the dose from 2.4 mg to 7.2 mg is both safe and more effective. Participants in the trials were randomly assigned to receive either the 7.2 mg dose, the standard 2.4 mg dose, or a placebo over 72 weeks. All groups also received lifestyle interventions such as dietary counseling and increased physical activity.

In adults without diabetes, those receiving the 7.2 mg dose lost an average of nearly 19% of their body weight—compared to 16% with the 2.4 mg dose 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%. Improvements were also seen in blood pressure, blood sugar, cholesterol, and waist circumference. In adults with obesity and T2D, the higher dose led to an average 13% weight loss versus 10% with 2.4 mg and 3.9% with placebo, along with significant metabolic improvements.

The higher dose was generally well tolerated, with the most common side effects being gastrointestinal issues like nausea and diarrhoea, and occasional tingling sensations. “Most side effects were manageable, resolved over time, and did not lead to participants dropping out of the trial.” Importantly, there was no increase in serious adverse events or hypoglycaemia with the higher dose.

In conclusion, the findings point to a potentially transformative option for managing obesity and related health risks. While long-term effects still need further study, the results mark a significant step forward in the treatment of obesity and T2D.

Reference: Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial, Wharton, Sean et al., The Lancet Diabetes & Endocrinology, Volume 0, Issue 0