Higher dose of semaglutide increases weight loss, metabolic benefits
Tripling the standard amount could safely treat patients with greater weight reduction goals, clinical trial led by UTSW researcher shows
DALLAS – Sept. 15, 2025 – 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 multicenter 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 patients 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 Ildiko Lingvay, M.D., M.P.H., M.S.C.S., 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 characterized by high blood sugar levels, insulin resistance, and a relative lack of insulin.
The class of medications called glucagon-like peptide-1 receptor agonists (GLP-1RAs) was first authorized in the early 2000s and includes semaglutide, which gained Food and Drug Administration (FDA) approval in 2017 for patients with Type 2 diabetes. These medications have been shown to be beneficial in treating Type 2 diabetes, and several medications in this class have also been permitted for chronic weight management as well as cardiovascular risk reduction.
Although patients with obesity can experience substantial benefits from a weekly injection of 2.4 milligrams (mg) of semaglutide – the currently approved dose taken by patients in the U.S. and the European Union – many still don’t achieve their weight-loss goals, Dr. Lingvay explained. Dose modeling research suggested that patients 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 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 patients – followed by medical teams at 68 sites in eight countries across Europe, southern Africa, and North America, including UTSW – stayed on these regimens for 72 weeks. They also received counseling 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 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% of their starting weight, compared with 3.9%. However, those taking the higher dose lost even more weight, 13.2% on average. Those in the higher dose group were also significantly more likely to reach weight reductions of up to 20% 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 patients lost 25% or more of their starting weight on the higher dose of semaglutide, compared with only 15% 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 patients on either dose and about a quarter of patients 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% of patients taking the higher dose in both trials experienced this effect, compared with about 5% 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 patient safety.
Both studies were funded by Novo Nordisk A/S. Dr. Lingvay receives personal consulting compensation from Novo Nordisk.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 24 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.