Higher-Dose Semaglutide Achieves Significant Weight Reduction in Adults with Obesity

In the 72-week, randomized, double-blinded, parallel-group, placebo-controlled STEP UP phase 3b trial (NCT05646706), individuals taking 2.4 mg of semaglutide (Wegovy; Novo Nordisk) and an investigational 7.2 mg dose of semaglutide lost an average of 21% of their body weight. According to data presented at ObesityWeek, held from November 4 to 7 in Atlanta, GA, semaglutide also reduced individuals' risk of obesity-related complications.^1,2

“These new results demonstrate that most people on [semaglutide] who achieve certain BMI and waist targets also benefit when it comes to lowering their cardiovascular risk factors,” Emil Kongshøj Larsen, executive vice president and head of International Operations at Novo Nordisk, said in a news release.¹

Semaglutide Indications

Semaglutide is FDA approved for use with a reduced-calorie diet and increased physical activity to lower the risk of major adverse cardiovascular events in adults with cardiovascular disease and either obesity or overweight. It is also indicated for long-term weight reduction in adults and adolescents aged 12 years and older with obesity or in adults who are overweight with at least 1 weight-related condition. Additionally, semaglutide has received accelerated approval for treating noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) in adults with moderate to advanced liver fibrosis.¹

Clinical Trial Results from STEP UP

Two trials, STEP UP and STEP UP T2D, have been completed to evaluate the efficacy and safety of 7.2 mg of semaglutide in individuals with obesity, both with and without type 2 diabetes (T2D).¹

The STEP UP trial evaluated semaglutide 7.2 mg compared with semaglutide 2.4 mg and placebo in 1407 adults with obesity and without diabetes. This trial focused on weight loss and the number of individuals achieving 10% to 25% reductions. The parallel STEP UP T2D trial included a total of 512 adults with obesity and T2D, assessing the superiority of semaglutide 7.2 mg compared with a placebo for weight loss.¹

In this current STEP UP sub-analysis that was shared at ObesityWeek, researchers noted that more individuals who received semaglutide achieved a target body mass index (BMI) of less than 27 and a waist-to-height ratio of less than 0.53 (19.5% for semaglutide 7.2 mg and 13.2% for semaglutide 2.4 mg) compared to placebo. Individuals treated with semaglutide who achieved both treatment targets achieved healthy levels for 2 or more cardiovascular risk factors, such as blood pressure, cholesterol, and glucose levels.¹

“This shows the efficacy of [semaglutide] in not only helping people lose excess weight but also preventing obesity-related complications and improving overall health. The risk of developing serious complications such as cardiovascular, kidney and liver diseases increases for people living with overweight or obesity,” Larsen said.¹

The STEP UP trial also found that a higher dose of semaglutide led to an average weight loss of 21%, with one-third of participants losing 25% or more of their body weight. Researchers noted that this provides a new treatment option to help individuals with obesity reach their weight and health goals.¹

Further results demonstrated that over half of adults who achieved both BMI and waist-to-height ratio targets reached healthy levels for risk factors, indicating a low risk of cardiovascular disease.¹

“The use of BMI and waist-to-height ratio targets has been shown to be associated with a lower risk of obesity-related complications,” Carel le Roux, University College Dublin, Ireland, said in the news release.¹

The findings suggest that most individuals treated with semaglutide achieved a BMI under 27 and a waist-to-height ratio less than 0.53 and had their blood pressure, cholesterol, and glucose levels return to healthy levels.¹

“This new STEP UP analysis reinforces the health benefits we have come to expect of semaglutide, such as cardiovascular protection, demonstrating its power in helping people with the disease of obesity achieve meaningful weight loss and health gains,” Roux concluded.¹

REFERENCES

1. Novo Nordisk Wegovy® users achieved waist and BMI targets linked to improved health and low risk of obesity-related complications. News release. Novo Nordisk. November 5, 2025. Accessed November 11, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916449

2. A Research Study to See How Semaglutide Helps People With Excess Weight, Lose Weight (STEP UP) (STEP UP). Novo Nordisk. Updated October 22, 2025. Accessed November 11, 2025. https://clinicaltrials.gov/study/NCT05646706