Higher-dose semaglutide Wegovy may help people lose up to 25% of body weight

A larger dose of the weight-loss medicine semaglutide, more widely recognised by its brand name Wegovy, could enable people to lose as much as 25% of their body weight without a heightened risk of serious adverse effects. The evidence comes from two clinical trials published recently.

Semaglutide is already known to support weight loss. However, even at the medicine’s highest authorised dose, weight reduction commonly levels off after roughly a year of treatment. As a result, some patients may fall short of their target weight loss.

Researchers therefore examined whether increasing the dose could improve results without causing severe side effects.

Higher-dose semaglutide and weight loss

In the first trial, the researchers assessed a 7.2mg dose of semaglutide in adults living with obesity. This amount is three times the currently approved 2.4mg dose used in Wegovy. For 72 weeks, participants were randomly allocated to receive the higher dose, the usual dose or a placebo injection once weekly.

They were also advised to cut their daily energy intake by approximately 500 calories and to increase weekly physical activity, with a target of about 150 minutes.

Among participants who followed the treatment plan fully, those given 7.2mg lost nearly 21% of their body weight on average. This compared with 17.5% among people receiving the standard dose. The placebo group lost only 2.4% of body weight.

About 33% of participants taking the larger dose achieved particularly substantial weight loss, shedding at least 25% of their overall body weight. That proportion was around twice that recorded in the standard-dose group, in which just under 17% reached this level of weight loss.

People treated with semaglutide also experienced more pronounced improvements in cardiometabolic health than those who received placebo alone.

As expected, adverse effects occurred more often with the higher semaglutide dose than with the lower dose. Gastrointestinal symptoms, including nausea and diarrhoea, were the most frequently reported.

Gastrointestinal problems led around 3% of people using the higher dose and 2% of those using the standard dose to discontinue the medicine.

Semaglutide dose in type 2 diabetes

The second trial explored the effects of a larger semaglutide dose in people with type 2 diabetes.

It is well established that people with type 2 diabetes generally lose less weight while taking semaglutide than people without diabetes, although the reason remains unclear. The second study consequently investigated whether a higher semaglutide dose could still produce meaningful weight loss in people with type 2 diabetes.

This study enrolled 512 participants who had both obesity and type 2 diabetes, using exactly the same study design as the earlier trial.

Participants receiving 7.2mg of semaglutide lost slightly more than 13% of their body weight. Those in the standard-dose group lost around 10%, whereas the placebo group lost just under 4% of their total body weight.

The 7.2mg dose also delivered measurable metabolic-health benefits beyond weight loss. Average waist circumference was 6.5cm lower than in the placebo group. Blood glucose levels, measured using HbA1c as an indicator of diabetes control, declined by nearly 2% among participants taking the higher dose.

Gastrointestinal symptoms were again the most common side effects among people using semaglutide, and around 6% of the trial’s participants withdrew because of these side effects.

Patient benefit

Semaglutide aids weight loss by copying the action of the body’s naturally occurring GLP-1 hormone, which helps to regulate appetite and blood sugar. These medicines influence brain pathways involved in food intake and energy balance, reducing hunger and creating an earlier feeling of fullness, or satiety, after meals. This may help people eat less and, in turn, lose weight.

Larger doses of semaglutide may produce greater weight loss by activating appetite-regulating areas of the brain more strongly, reducing hunger while increasing the sensation of fullness. They also slow the emptying of the stomach more effectively, which can further lower total food consumption.

Together, the two trials indicate that a higher semaglutide dose is both safe and highly effective. Access to a larger dose could give patients additional choices for weight management and blood-sugar control. It may also provide an option for people who do not respond to the usual 2.4mg dose or whose weight loss has reached a plateau.

The findings also suggest semaglutide could compete with other weight-loss drugs, including tirzepatide (Mounjaro).

In a previous direct comparison trial, a 10gm–15mg dose of tirzepatide produced 20% body-weight loss in participants, while the standard semaglutide dose led to approximately 14% body-weight loss.

These newer studies, however, indicate that a higher dose of semaglutide can achieve similar levels of weight loss.

The results could also prompt questions over whether increasing doses might become a future standard of care for obesity treatment.

Martin Whyte, Associate Professor of Metabolic Medicine, University of Surrey

This article is republished from The Conversation under a Creative Commons licence. Read the original article.