Two studies published in The Lancet Diabetes & Endocrinology looks at the effect of higher doses of semaglutide on weight loss in adults with obesity.
Prof Lora Heisler, Director of Research, Rowett Institute, University of Aberdeen, Rowett Institute, University of Aberdeen, said:
“This study investigated whether a once weekly injection with a higher dose of semaglutide (the active ingredient of Wegovy and Ozempic) produced greater therapeutic benefits for patients living with obesity and type 2 diabetes compared to current doses. Advantages of the two studies is that they were conducted in different countries and included participants with different nationalities. What they found is that the higher dose of semaglutide (7.2 mg) led to an average of 18.7% weight loss compared with placebo. Around half of patients lost 20% or more weight over the study period. This higher dose of semaglutide (7.2 mg) was associated with more side effects, in particular GI side effects such as nausea, vomiting and constipation compared with placebo. Most of the weight loss with semaglutide was body fat. However, something to follow up in future is whether some muscle is also lost with this higher degree of weight loss produced by semaglutide. The higher dose of semaglutide used in this study of 7.2 mg was quite a bit higher compared to the current highest dose of 2.0-2.4 mg that has been rigorously tested for safety and is available to patients now. Having more treatment options available to patients is a positive step forward. Some patients may need a higher dose of semaglutide to meet their treatment goals. However, this higher dose of semaglutide (7.2 mg) is still under investigation and its benefit needs to be considered alongside safety by regulatory bodies. Every person is different and what is right for one person may not be right for another. It is important for patients to discuss treatment with their health care provider to find out what is best for them, if this higher dose of semaglutide does get approved for widespread use in future.”
Dr Simon Cork, Senior Lecturer in Physiology, Anglia Ruskin University (ARU), said:
“These two studies investigated the effects of higher dose semaglutide on body weight in patients with obesity with and without type 2 diabetes. The effects of high dose semaglutide were compared against placebo and against a standard dose of semaglutide (marketed as Wegovy).
“The studies demonstrate that the higher dose of semaglutide results in reductions in body weight, BMI and systolic blood pressure compared to placebo, but the results are only statistically significant against the standard dose in patients who do not have type 2 diabetes (although it’s important to note that the studies were designed to compare high dose against placebo only, and not sufficiently powered to compare against the standard dose). Interestingly ,in patients without obesity, twice as many patients (33% vs 16%) lost over 25% of their body weight on higher dose semaglutide compared to lower dose. This suggests that patients with higher body mass, who would benefit most from more substantial weight loss, may benefit more from high dose semaglutide than that which is currently available.
“It is noteworthy, but not surprising that more patients on the higher dose experienced side effects (such as nausea and vomiting) compared to the lower dose.
“Whether patients will get access to this higher dose semaglutide remains to be seen, but Novo Nordisk (who manufacture semaglutide) will no doubt be conscious of the increasing competition in the weight loss arena, with drugs such as Mounjaro resulting in superior weight loss compared with Wegovy, and further medications also demonstrating greater weight loss effects, or in pill form also in late stage clinical trials.”
Paper 1: ‘Once-weekly semaglutide 7·2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial’ by Ildiko Lingvay et al. was published in The Lancet Diabetes & Endocrinology at 23.30 UK time Sunday 14th September 2025.
Paper 2: ‘Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial’ by Sean Wharton et al. was published in The Lancet Diabetes & Endocrinology at 23.30 UK time Sunday 14th September 2025.
Declared interests
Dr Simon Cork: No COIs.
Prof Lora Heisler: Prof Heisler is a consultant, sits on the Scientific Advisory Board and receives research funding from various pharmaceutical companies, but not Novo Nordisk (Wegovy).