Novo Nordisk is presenting a new sub-analysis from the large clinical trial STEP UP at the European Congress on Obesity (ECO) on 12-15 May in Istanbul, Türkiye, showing that the higher dose of the weight loss drug Wegovy® is highly effective at helping people with obesity lose significant amounts of weight regardless of how quickly their body responds to the treatment1.

Moreover, a separate STEP UP sub-analysis presented at ECO shows that most of the weight loss with Wegovy® was coming from body fat, and most of the muscle mass was kept2.

The STEP UP trial in people with obesity tested the higher dose of semaglutide (7.2 mg) against the 2.4 mg dose and placebo over 72 weeks in over 1,400 adults living with obesity without type 2 diabetes3. The results were striking. On average, people taking the 7.2 mg dose lost 21% of their total body weight – the equivalent of around 23 kg for the average person in the trial who weighed 113 kg before starting treatment with semaglutide3. People on the 2.4 mg dose lost about 17.5% within 72 weeks, while those on the placebo lost 2.4%3. The 21% weight loss with semaglutide 7.2 mg was achieved with a safety and tolerability profile consistent with the 2.4 mg semaglutide dose3.

A new analysis has revealed insights into how fast and how much weight loss people who respond differently can expect, and the findings are presented at ECO. ‘Early responders' were identified as people who lost 15% or more of their body weight within just the first 24 weeks (about 6 months) of treatment1. About 1 in 4 people (27%) taking the 7.2 mg dose of Wegovy® had an early response, compared with about 1 in 5 (21%) on the 2.4 mg dose and 3% on placebo1. The early responder group lost 27.7% of their body weight at week 721.

STEP UP weight-loss results1,3

 Semaglutide 7.2 mgSemaglutide 2.4 mgPlacebo
STEP UP primary results   
Average weight loss % across all groups20.7%17.5%2.4%
STEP UP sub-analysis   
Average weight loss % in early responders (≥15% loss by week 24)27.7% (in 26.9% of participants)24.8% (in 20.9% of participants)-
Average weight loss in Responders (excluding early responders)15.4%13.2%-

"Obesity as a chronic disease demands lifelong, holistic treatment. Early weight loss may indicate who is likely to achieve the most weight loss from semaglutide – but it is important to highlight that those without an ‘early' treatment response still experience a substantial and clinically meaningful weight loss. These new insights from the STEP UP sub-analysis presented at ECO can help healthcare professionals with managing expatiations and setting goals with their patients when initiating obesity medications and potentially support long-term persistence to treatments," said Dr Dror Dicker, associate clinical professor of Internal Medicine at The Faculty of Medicine and Health Sciences, Tel-Aviv University, Israel.

Improved muscle health
Another secondary analysis from a sub-population (55 participants) in the STEP UP trial studied body scan images (MRI) showing that 84% of the lost weight with semaglutide (2.4 and 7.2 mg) was due to a reduction in fat mass2. The abdominal visceral fat was reduced by over 30% with semaglutide2. Muscle mass was reduced by only 10% compared to baseline with semaglutide, and importantly, this was accompanied by improved muscle health, as assessed by the amount of muscle fat2. Both visceral and muscle fat are highly associated with the risk of cardiometabolic complications4-6. This means the drug was highly effective at specifically targeting fat in different body depots. Importantly, participants taking semaglutide maintained their functional muscle strength, even as they lost significant weight2. Muscle function was measured using a 30-second sit-to-stand test, which showed the same functional muscle strength in both the semaglutide and placebo groups before and after treatment2. Together, these results underscore the healthy improvements seen with semaglutide in body composition and muscle function2.

"The analyses from STEP UP presented at ECO are really promising, further highlighting the potential of the higher dose of Wegovy® to achieve substantial weight loss. Importantly, for individuals focused on losing weight, the goal is often to reduce fat rather than muscle mass. These studies show that weight loss with Wegovy® is predominantly driven by reductions in fat, while muscle function is preserved. This is great news for people living with obesity," said Emil Kongshøj Larsen, executive vice president and head of International Operations at Novo Nordisk.

The results of the STEP UP sub-analysis of semaglutide's improvement of body composition have been submitted for publication to a scientific journal.