Detailed results from the Phase IIIb STEP UP trial (NCT05646706) demonstrated that an investigational 7.2 mg dose of Wegovy (semaglutide) produced a mean weight loss of 21% in adults with obesity and without diabetes along with a tolerable safety profile.

STEP UP Trial Shows Efficacy of Higher Dose Wegovy for Weight Loss in Adults With Obesity Without Diabetes

These data, presented at the 2025 American Diabetes Association Scientific Sessions, reinforce the dose-dependent efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists and may broaden clinical options for obesity management, according to the study investigators.^1,2

“The STEP UP trial demonstrated that we can increase the dose of semaglutide and achieve greater weight loss than previously seen, and in line with semaglutide’s established safety profile. This may offer another option to people who do not attain their weight goals,” lead study author Sean Wharton, medical director of the Wharton Medical Clinic, Canada, said in a press release. “We are already aware that semaglutide can have health benefits for people with heart disease, liver disease, knee osteoarthritis, type 2 diabetes and prediabetes. These findings help to give patients with obesity more options for improvements in their weight and overall health.”¹

Semaglutide, a GLP-1 receptor agonist, was initially approved in June 2021 for chronic weight management in individuals with obesity or overweight and at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol, in addition to diet and increased exercise.³

Semaglutide has also been approved by the FDA in both long-acting injectable (Wegovy and Ozempic) and daily oral tablet (Rybelsus) formulations. In March 2024, Wegovy 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

STEP UP Trial Design and Patient Population

• STEP UP is a randomized, double-blind, parallel-group, placebo-controlled, superiority study evaluating the efficacy of semaglutide at a dose of 7.2 mg compared to semaglutide at a dose 2.4 mg and placebo as an adjunct to lifestyle intervention.
• Investigators enrolled 1,407 adults 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 compared to placebo.
• Key secondary endpoints included the proportion of patients achieving weight loss of 10%, 15%, 20%, and 25%.
• Patients enrolled in STEP UP also received counseling from study staff regarding how to establish a healthy diet and how to increase physical activity.

Key Efficacy Results From STEP UP

• Results show the semaglutide 7.2 mg cohort achieved weight loss of 20.7% compared to 17.5% in the semaglutide 2.4 mg cohort and 2.4% in the placebo cohort.
• A total of 93.2% of patients in the semaglutide 7.2 mg cohort achieved weight loss of 5% or more compared to 92.5% in the semaglutide 2.4 mg cohort and 35.7% in the placebo cohort.
• Further, data show that when disregarding treatment adherence, the semaglutide 7.2 mg cohort achieved weight loss of 18.7% compared to 3.9% in the placebo cohort, with 90.7% of patients in the semaglutide 7.2 mg cohort achieving 5% or more weight loss compared to 36.8% in the placebo cohort.

Safety and Tolerability Profile of Semaglutide 7.2 mg

• In terms of safety, the most frequently reported adverse events (AEs) were gastrointestinal in nature, most of which were mild to moderate in severity. These AEs primarily occurred during dose escalation and faded as the trial progressed.
• A total of 3.3% of patients in the semaglutide 7.2 mg cohort discontinued treatment because of gastrointestinal AEs compared to 2.0% in the semaglutide 2.4 mg cohort and 0% in placebo cohort.

Implications for Obesity Treatment and Next Steps

“With these results, semaglutide reaffirms its significant weight loss for people with obesity. The STEP UP trial delivers a substantial weight loss of over 20%, in addition to health benefits previously demonstrated with semaglutide,” Ludovic Helfgott, executive vice president of Product & Portfolio Strategy at Novo Nordisk, said in the release. “As pioneers in obesity, we continue to develop new innovative treatments to fit the needs and preferences of people living with obesity. This includes maximising the value of semaglutide for individuals, healthcare systems and society, and developing a new oral formulation of Wegovy that, pending FDA approval, can become the first GLP-1 pill to offer double-digit weight loss.”¹

References

1. Novo Nordisk: Higher dose of Wegovy® provided average weight loss of 21% in people with obesity – with a third achieving 25% or more – according to data presented at ADA. News release. Novo Nordisk. June 20, 2025. Accessed June 25, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916352

2. A Research Study to See How Semaglutide Helps People With Excess Weight, Lose Weight (STEP UP). ClinicalTrials.gov. Updated April 24, 2025. Accessed June 25, 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 June 25, 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 June 25, 2025. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=167031