Novo Nordisk's investigational higher dose of semaglutide (7.2 mg) has demonstrated superior weight loss compared to the standard 2.4 mg dose (Wegovy) and placebo in the Phase 3b STEP UP trial. The 72-week trial, involving 1,407 adults with obesity, showed that participants on the 7.2 mg dose achieved a statistically significant and clinically meaningful reduction in body weight. This development could potentially offer a more effective treatment option for individuals struggling with obesity.
The STEP UP trial was a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of subcutaneous semaglutide 7.2 mg compared to semaglutide 2.4 mg and placebo, all administered once weekly in conjunction with lifestyle intervention. The primary endpoint was to demonstrate the superiority of semaglutide 7.2 mg against placebo on weight loss at week 72.
Key Findings from the STEP UP Trial
When evaluating the effects of treatment if all people adhered to treatment from a mean baseline body weight of 113 kg, participants treated with semaglutide 7.2 mg achieved a superior weight loss of 20.7% after 72 weeks compared to a reduction of 17.5% with semaglutide 2.4 mg and 2.4% with placebo. Furthermore, 33.2% of those who received semaglutide 7.2 mg achieved a weight loss of 25% or more after 72 weeks, compared to 16.7% with semaglutide 2.4 mg and 0.0% with placebo.
Even when applying the treatment policy estimand, which considers treatment effect regardless of adherence, individuals treated with semaglutide 7.2 mg still achieved a superior weight loss of 18.7% compared to a reduction of 15.6% with semaglutide 2.4 mg and 3.9% with placebo.
Safety and Tolerability
The safety profile of semaglutide 7.2 mg in the STEP UP trial appeared to be consistent with the known profile of the GLP-1 receptor agonist class. The most common adverse events reported were gastrointestinal in nature, with the vast majority being mild to moderate and diminishing over time.
Expert Commentary
"We are very pleased to demonstrate 20.7% weight loss and to see that 33% of patients achieved more than 25% weight loss with semaglutide 7.2 mg, with a safety and tolerability profile comparable to semaglutide 2.4 mg," said Martin Holst Lange, executive vice president for Development at Novo Nordisk. "Results from STEP UP further strengthen the clinical profile of semaglutide for the treatment of obesity, in addition to the health benefits already established with Wegovy, including cardiovascular risk reduction as seen in SELECT."
Ongoing Research
Novo Nordisk is also investigating semaglutide 7.2 mg in the STEP UP T2D trial, which focuses on adults with type 2 diabetes and obesity. Results from this trial are expected in the coming months. Detailed findings from the STEP UP trial are slated for presentation at a scientific conference in 2025.
