STEP UP Trial Shows Semaglutide 7.2 mg Achieves Superior Weight Loss vs. 2.4 mg, Placebo

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Topline findings from the 72-week STEP UP trial (NCT05646706) show that semaglutide at a dose of 7.2 mg produced superior weight loss compared to semaglutide at a dose of 2.4 mg and placebo.^1,2 This is the first of two trials evaluating the effectiveness of semaglutide at a dose of 7.2 mg, with the other being the ongoing, 72-week STEP UP T2D trial. In a press release, Novo Nordisk stated that it anticipates presenting detailed data from the STEP UP trial at a scientific conference later this year.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist (RA). It was initially approved in June 2021 for chronic weight management in those with obesity or overweight and at least one weight-related condition, including high blood pressure, type 2 diabetes, or high cholesterol, in addition to diet and increased exercise.³ 

Semaglutide has been approved by the FDA in both long-acting injectable (Wegovy and Ozempic) and daily oral tablet (Rybelsus) formulations. In March 2024, Wegovy (semaglutide) was approved by the FDA to reduce the risk of major adverse cardiovascular events in adults with known heart disease and with obesity or overweight, in addition to a reduced calorie diet and increased physical activity.⁴

Trial Design

STEP UP is a randomized, double-blind, parallel-group, placebo-controlled, superiority study comparing the effectiveness of semaglutide 7.2 mg vs. semaglutide 2.4 mg and placebo as an adjunct to lifestyle intervention. Investigators enrolled 1,407 adult patients with a BMI ≥30 kg/m2 and without diabetes.

The trial’s primary endpoint was to establish superiority in weight loss of semaglutide 7.2 mg vs. placebo, with key secondary endpoints that included number of patients who achieve 10%, 15%, 20% and 25% weight loss, respectively. Patients enrolled in STEP UP will also receive counseling from study staff regarding how to establish a healthy diet and to increase physical activity.

STEP UP T2D is evaluating semaglutide 7.2 mg in 512 adult patients with obesity and type 2 diabetes. That trial’s primary endpoint is to establish the superiority of semaglutide 7.2 mg vs. placebo in weight loss.

Trial Results

Among patients who were adherent to the trial regimen, from a mean baseline body weight of 113 kg, patients in the semaglutide 7.2 mg cohort experienced weight loss of 20.7% after 72 weeks, compared to 17.5% in the semaglutide 2.4 mg cohort and 2.4% in the placebo cohort. Further, 33.2% of patients in the semaglutide 7.2 mg cohort experienced weight loss of 25% or greater at 72 weeks, compared with 16.7% in the semaglutide 2.4 mg cohort and 0.0% in the placebo cohort. In terms of the treatment policy estimand, patients in the semaglutide 7.2 mg cohort experienced weight loss of 18.7% vs. 15.6% in the semaglutide 2.4 mg cohort and 3.9% in the placebo cohort.

Semaglutide 7.2 mg was reported to have a safe and well-tolerated profile, with the most frequently reported adverse events (AEs) being gastrointestinal in nature and mild to moderate in severity. These AEs lessened over time, which Novo Nordisk stated is consistent with the GLP-1 receptor agonist class.

The company added that findings from STEP UP T2D are anticipated to be released over the next few months.

“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,” Martin Holst Lange, executive vice president of Development at Novo Nordisk, stated in the release. “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.”¹

References

1. Novo Nordisk A/S: Semaglutide 7.2 mg s.c. achieved 20.7% weight loss in the STEP UP obesity trial, and 18.7% regardless of treatment adherence. News release. 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. A Research Study to See How Semaglutide Helps People With Excess Weight, Lose Weight (STEP UP). ClinicalTrials.gov. Updated December 12, 2024. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT05646706

3. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014. FDA. News release. June 4, 2021. Accessed January 17, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014

4. Wegovy® receives FDA approval for cardiovascular risk reduction in adults with known heart disease and overweight or obesity. Novo Nordisk. News release. March 8, 2024. Accessed January 17, 2025. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=167031