Weight loss drug semaglutide shown to be safe and potentialy more effective at higher dose – new findings

A higher dose of the weight loss drug semaglutide (better known by its brand name Wegovy) may help people lose up to 25% of their body weight – without the risk of severe side-effects. These findings are based on the results of two recently published clinical trials.

Semaglutide has proven to be effective in helping people lose weight. But weight loss tends to plateau after about one year of use – even when taking the highest approved dose of the drug. This means patients may not reach their weight loss goals.

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So researchers set out to understand whether a higher dose can be effective without the risk of severe side-effects.

In the first trial, researchers studied the effect of a 7.2mg dose of semaglutide in adults with obesity. This is three times the currently approved 2.4mg dose found in Wegovy. Participants were randomly assigned to either receive the higher dose, the standard dose or a placebo drug once a week for a period of 72 weeks.

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Participants were also told to reduce their daily calorie intake by around 500 calories per day and increase the amount of physical activity they did each week (aiming for around 150 minutes).

The participants who received the 7.2mg dose lost an average of nearly 21% of their body weight – compared with 17.5% for those on the standard dose. Participants who took the placebo only lost 2.4% of their body weight. These figures are based on those who fully adhered to the treatment regimen.

Around 33% of the participants on the higher dose also experienced very high levels of weight loss – losing 25% or more of their total body weight. This is roughly double the proportion seen in the standard-dose group, where just under 17% achieved this degree of weight loss.

The participants who used semaglutide also saw greater improvements in their cardiometabolic health compared to those who only received the placebo.

As might be anticipated, side-effects were more common in people taking the higher dose of semaglutide than those taking the lower dose. The most common side-effects were gastrointestinal issues, such as nausea or diarrhoea. Around 3% of participants using the higher dose and 2% of participants using the standard dose stopped using the drug because of these gastrointestinal issues.

A second trial then investigated what effect a higher dose of semaglutide would have in people with type 2 diabetes.

It’s well established that people with type 2 diabetes tend to lose less weight on semaglutide compared to those without diabetes. It’s not currently known why this is. So the second trial sought to understand whether a higher dose of semaglutide would also have a significant effect on weight loss in people with type 2 diabetes.

This time they recruited 512 participants with obesity who also had type 2 diabetes. They used the exact same study design as they did in the previous study.

Those treated with 7.2mg of semaglutide lost just over 13% of their body weight. The standard dose group lost around 10% of their body weight, while the placebo group lost just under 4% of their total body weight.

Beyond weight loss, the 7.2mg dose of semaglutide brought measurable improvements in metabolic health. On average, waist circumference decreased by 6.5cm compared to the placebo group. Blood glucose levels (HbA1c, a measure of diabetes control) also fell by nearly 2% in those taking the higher dose.

Gastroinstestinal problems were again the most commonly experienced side-effects in those taking semaglutide – with around 6% of the study’s participants stopping the trial because of these side-effects.

Patient benefit

Semaglutide promotes weight loss by mimicking the body’s natural GLP-1 hormone, which helps regulate blood sugar and appetite. These drugs act on brain pathways that control energy balance and food intake, leading to reduced hunger and an earlier sense of fullness (satiety) after eating. This can help people to eat less, leading to weight loss.

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Higher doses of semaglutide lead to greater weight loss by more strongly activating the brain regions that control appetite, resulting in reduced hunger and increased feelings of fullness. They also slow stomach emptying more effectively, helping to decrease overall food intake.

The results from these two trials show that a higher dose of semaglutide is both safe to use and very effective. Being able to use a higher dose of semaglutide offers more options for patients when it comes to managing their weight and controlling their blood sugar. It also gives an option to people who may not respond to the standard 2.4mg dose or whose weight loss may plateau.

These findings also show that semaglutide can compete against other weight loss drugs, such as tirzepatide (Mounjaro). In an earlier head-to-head trial, a 10gm-15mg dose of tirzepatide resulted in a 20% loss of body weight in participants – while a standard dose of semaglutide only resulted in an approximately 14% loss in body weight. But these recent studies now show that a higher dose of semaglutide can lead to comparable levels of weight loss.

These results may also raise questions about whether dose escalation may become a future standard of care in obesity treatment.