Higher dose of semaglutide increases weight loss, metabolic benefits
Tripling the standard dose of semaglutide, a popular drug prescribed to treat obesity, led to significantly greater weight loss and associated metabolic benefits without increased risk of serious side effects, a multicentre clinical trial led by a UT Southwestern Medical Center researcher shows.
The findings published in The Lancet Diabetes & Endocrinology, along with results from a related clinical trial published concurrently, suggest that people seeking to lose more weight can safely take a higher semaglutide dose than typically prescribed.
“Semaglutide and other drugs in its class have been life-changing for people living with obesity around the world. Our new findings suggest that increasing the dose can lead to even greater benefits and may be appropriate for some patients,” said study leader Dr Ildiko Lingvay, Professor of Internal Medicine in the Division of Endocrinology and in the Peter O’Donnell Jr School of Public Health at UT Southwestern.
The obesity epidemic continues to grow, with nearly 1 billion people worldwide living with this condition, according to the World Health Organization. Obesity contributes to the development and progression of type 2 diabetes, a disease characterised by high blood sugar levels, insulin resistance and a relative lack of insulin.
Although people living with obesity can experience substantial benefits from a weekly injection of 2.4 milligrams (mg) of semaglutide – the currently approved dose taken by people in the U.S. and the European Union – many still don’t achieve their weight-loss goals. Dose modelling research suggested that individuals might receive even more benefits with little extra risk at a 7.2 mg dose, a concept that was tested in the STEP UP trials (STEP UP Obesity and STEP UP Diabetes).
In the phase 3b STEP UP Diabetes trial, researchers tracked 512 adults living with obesity and type 2 diabetes assigned to three groups: 307 who took 7.2 mg of semaglutide weekly; 103 who took 2.4 mg weekly; and 102 who took a placebo. The participants – followed by medical teams at 68 sites in eight countries across Europe, southern Africa, and North America, including UTSW – stayed on these regimes for 72 weeks. They also received counselling every four weeks to support a reduced-calorie diet and increased physical activity.
As in earlier trials evaluating a 2.4 mg weekly dose of semaglutide in people living with obesity and type 2 diabetes, results showed that participants on that dose lost significantly more body weight than those on the placebo – an average of 10.4 per cent of their starting weight, compared with 3.9 per cent.
However, those taking the higher dose lost even more weight, 13.2 per cent on average. Those in the higher dose group were also significantly more likely to reach weight reductions of up to 20 per cent of their waist circumference (a clinically meaningful measure of cardiometabolic risk) and improve their HbA1C (a measure of blood sugar control) compared with the other two groups.
The STEP UP Obesity trial enrolled people living with obesity but without type 2 diabetes. In this study, nearly a third of people lost 25 per cent or more of their starting weight on the higher dose of semaglutide, compared with only 15 per cent who lost that amount on 2.4 mg and none on the placebo.
In both trials, the most common side effect was gastrointestinal symptoms, which affected about half of the participants on either dose and about a quarter of people on the placebo. These side effects were typically present while participants were gradually increasing their dose in the first few weeks of the trial and tended to improve thereafter.
The only side effect experienced by more of those on the higher semaglutide dose was dysaesthesia, which alters touch sensation. About 20 per cent of people taking the higher dose in both trials experienced this effect, compared with about 5 per cent of those on the lower dose. Together, Dr Lingvay said, the results reinforce the promise of semaglutide and other GLP-1RAs with benefits that appear to increase at a higher dose without compromising safety.
Both studies were funded by Novo Nordisk A/S. Dr Lingvay receives personal consulting compensation from Novo Nordisk.