By Dr. Asnat Raziel, specialist in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal
The STEP UP trial: Wegovy moves up a level
The STEP UP trial changed what we knew about the maximum dose of Wegovy. For years we treated 2.4 mg as the ceiling. However, in 2026 the picture changed. Regulators in Europe and the United States approved a new dose of semaglutide, 7.2 mg a week, based on the trial’s results. In addition, new analyses show who responds especially well and what the weight loss is made of.
What did the STEP UP trial test?
The Lancet Diabetes & Endocrinology published the STEP UP trial in September 2025. It is a randomized, double-blind phase 3b trial run at 95 centers in 11 countries. It enrolled 1,407 adults with a BMI, or body mass index, of 30 or more, without type 2 diabetes. Average starting weight was 113 kg.
The researchers divided participants into three groups, in a 5:1:1 ratio:
- Semaglutide 7.2 mg once a week.
- Semaglutide 2.4 mg once a week.
- Placebo, a dummy treatment.
All participants also received lifestyle support, and follow-up lasted 72 weeks.
How much weight did people lose?
In the main analysis, which included all participants regardless of adherence, average weight loss was:
- 18.7% with 7.2 mg.
- 15.6% with 2.4 mg.
- 3.9% with placebo.
The difference between the two doses was statistically significant. In contrast, in the analysis that assumes all participants stayed on treatment, weight loss with 7.2 mg reached 20.7%, compared with 17.5% with 2.4 mg. In other words, a person weighing 100 kg could lose about 21 kg on average if they stay on treatment.
The STEP UP trial and losses of 25% or more
One of the most impressive findings is how many patients reached very large losses. Patients on 7.2 mg reached a 20% and a 25% loss more often than those on 2.4 mg. According to Novo Nordisk’s announcement of the FDA approval, 31.2% of patients on the high dose lost 25% or more of their weight, in the analysis assuming adherence. That is almost one in three.
What’s new: the early responders
In May 2026, further analyses of the trial were presented at the European Congress on Obesity, ECO. The researchers focused on early responders, meaning people who lost at least 15% of their weight within 24 weeks. On 7.2 mg, 26.9% of participants were early responders. By 72 weeks they reached an average loss of 27.7%, compared with 24.8% for early responders on 2.4 mg.
However, this does not mean that everyone who moves up to 7.2 mg will lose almost 28%. This is a subgroup that responded well in the first months. Still, the figure shows how large the response can be in some patients.
Does the weight loss come mainly from muscle?
This is one of the key questions in obesity drug treatment today. In an MRI analysis of 55 participants, about 84% of the weight lost with semaglutide came from fat. Visceral fat, the deep belly fat, fell by more than 30%. The full analysis, published in September 2026, showed a drop in the fat inside the thigh muscle. Thigh muscle volume fell slightly, but not significantly compared with placebo. On the other hand, participants kept the same number of chair stands in 30 seconds, so function stayed intact.
So even at the high dose, it is important to focus on protein and strength training. This limits the loss of lean mass, as I explained in my article on lean body mass on GLP-1 drugs.
The STEP UP trial and side effects
As expected, gastrointestinal side effects were common at the high dose. They occurred in 70.8% of patients on 7.2 mg, in 61.2% on 2.4 mg and in 42.8% on placebo. Most were the familiar type seen with GLP-1 drugs. You can read more in my guide to Wegovy side effects.
In addition, the researchers reported dysaesthesia, abnormal skin sensations such as tingling, burning or altered sensation. It occurred in 22.9% of patients on 7.2 mg, compared with 6.0% on 2.4 mg and 0.5% on placebo. By contrast, serious adverse events affected 6.8% on the high dose, 10.9% on 2.4 mg and 5.5% on placebo.
What about type 2 diabetes?
In parallel, the researchers ran the STEP UP T2D trial in 512 adults with obesity and type 2 diabetes. There, average weight loss with 7.2 mg was 13.2%, compared with 3.9% on placebo. HbA1c, average blood sugar over the past three months, also fell by 1.5% more than with placebo. As usual, weight loss in people with diabetes is somewhat more modest.
Where do things stand today?
In February 2026, the European Commission approved the 7.2 mg dose for adults with obesity. At first, patients took the dose as three 2.4 mg injections at the same time, once a week. In March 2026, the FDA approved Wegovy HD, a 7.2 mg pen. According to the US prescribing information, patients move up to this dose only after at least four weeks on 2.4 mg, when further weight loss is needed. In July 2026, the European Commission also approved a single pen for the 7.2 mg dose.
What does the STEP UP trial mean in practice?
It does not mean that every patient on Wegovy should move up to 7.2 mg. The 2.4 mg dose remains a very effective treatment for many, and some patients achieve excellent results even at lower doses. However, for patients with significant obesity who have not reached their goal, the high dose offers another option. That way, there is no need to conclude that “Wegovy has stopped working”. For a comparison of the high doses of different drugs, see my article Mounjaro vs. Wegovy.
This is part of a broader shift in obesity treatment. Less of one dose for everyone, and more tailoring of treatment intensity to each patient’s response. This approach is called treating to target, and it requires close medical follow-up.
This article provides general information and is not a substitute for personal medical advice.
References
Wegovy HD (semaglutide 7.2 mg) approved in the US, providing 20.7% mean weight loss
The European Commission approves more effective dose of injectable Wegovy for adults with obesity
