Semaglutide 7.2 mg Displays 20.7% Weight Loss in Phase 3b STEP UP Trial

Martin Holst Lange

Credit: Novo Nordisk

Topline results from a Phase 3b trial in the global STEP program demonstrated statistically significant and superior weight loss at 72 weeks with semaglutide 7.2 mg, compared with placebo, irrespective of treatment adherence.

Announced by Novo Nordisk on January 17, 2025, the randomized, double-blinded, parallel-group, placebo-controlled STEP UP trial evaluated the efficacy of semaglutide 7.2 mg to semaglutide 2.4 mg (Wegovy) and placebo in more than 1400 adults with obesity and without type 2 diabetes (T2D).¹

“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 [semaglutide 2.4 mg], including cardiovascular risk reduction as seen in SELECT,” Martin Holst Lange, executive vice president for development at Novo Nordisk, said a statement.¹

The US Food and Drug Administration (FDA) initally approved semaglutide 2.4 mg in June 2021, for chronic weight management in adults with obesity or overweight, marking a landmark approval for the glucagon-like peptide-1 receptor agonist (GLP-1 RA) class.² A label expansion in March 2024 added an indication for reduction of cardiovascular risk among adults with obesity or overweight, based on results from the SELECT trial.³

The primary objective of the STEP UP trial was to demonstrate the superiority of semaglutide 7.2 mg to placebo on weight loss. Key secondary endpoints followed up with the number of individuals achieving 10%, 15%, 20%, and 25% weight loss, respectively. A total of 1407 randomized adults, with a mean baseline body weight of 113 kg, were randomized to once-weekly semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo over 72 weeks, in conjunction with lifestyle intervention.¹

In assessment of the treatment effect, based on treatment adherence, results from STEP UP showed individuals treated with semaglutide 7.2 mg achieved a superior weight loss of 20.7% after 72 weeks, compared with 17.5% for semaglutide 2.4 mg and 2.4% for placebo. Approximately one-third (33.2%) of those who received semaglutide 7.2 achieved ≥25% weight loss after 72 weeks, compared with 16.7% for semaglutide 2.4 mg and 0% for placebo.

After application of the treatment policy estimand, individuals treated with semaglutide 7.2 mg exhibited a superior weight loss of 18.7%, compared with 15.6% for semaglutide 2.4 mg and 3.8% for placebo. Safety data from STEP UP demonstrated the tolerable profile of semaglutide 7.2 mg, with most signals mild-to-moderate gastrointestinal events, consistent with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) class.

Novo Nordisk announced more detailed results from STEP UP will be presented at a scientific conference in 2025. Results from the second Phase 3 trial evaluating semaglutide 7.2 mg in adults with T2D and obesity (STEP UP T2D) are anticipated in the coming months, according to the company.¹

“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,” Lange added.¹

References

1. _{Semaglutide 7.2 mg s.c. achieved 20.7% weight loss in the STEP UP obesity trial, and 18.7% regardless of treatment adherence. Novo Nordisk. January 17, 2025. Accessed January 17, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915087.}
2. _{Campbell P. Semaglutide (Wegovy) approved for chronic weight management in patients with obesity or overweight. HCP Live. April 17, 2023. Accessed January 17, 2025. https://www.hcplive.com/view/semaglutide-approved-for-chronic-weight-management-in-patients-with-obesity-or-overweight.}
3. _{Campbell P. Semaglutide (Wegovy) receives FDA label expansion to include cardiovascular risk reduction. HCP Live. March 8, 2024. Accessed January 17, 2025. https://www.hcplive.com/view/semaglutide-wegovy-receives-fda-label-expansion-to-include-cardiovascular-risk-reduction.}