Higher Doses Safely Led to Greater Weight Loss In New Study

• Researchers say higher doses of semaglutide weight loss medications can be effective in helping treat obesity.
• In two new studies, the researchers reported that people taking 7.2 mg doses of semaglutide lost more weight than people who took smaller doses or received a placebo.
• While GLP-1 medications can help with weight loss, experts recommend a healthy lifestyle that includes a balanced diet and daily exercise for healthy weight management.

A significantly higher dose of weight-loss drugs containing the active ingredient semaglutide can be more effective in helping people lose weight.

That’s according to two new studies published on September 14 in The Lancet Diabetes & Endocrinology journal.

In both clinical trials, participants who received a triple dose of semaglutide medication achieved slightly more weight loss than people taking a standard dose.

The weight loss was more significant when compared to study participants who were given a placebo.

In both trials, participants were advised on lifestyle factors such as diet and exercise. Novo Nordisk, the manufacturer of semaglutide medications like Ozempic and Wegovy, funded both trials.

The first study involved 1,407 people with obesity who did not have type 2 diabetes. About 73% of the participants were female. They had a mean age of 47 and a mean body mass index (BMI) of almost 40.

The participants were followed between January 2023 and November 2024 at 95 medical facilities in 11 countries.

The majority of the participants were prescribed to a regimen involving 7.2 mg weekly doses of semaglutide medication, triple the standard dose. The other subjects were given either 2.4 mg doses or a placebo.

In that study, researchers reported that people taking the 7.2 mg dose achieved an average weight loss of 19% compared to an average 16% weight loss for those taking the 2.4 mg dose and nearly 4% for those given the placebo.

The researchers added that about half of the participants on the 7.2 mg dose lost at least 20% of their body weight while a third lost at least 25% of their body weight.

They also reported that the higher dose group showed more benefits in:

The second study involved 512 people diagnosed with obesity and type 2 diabetes. About 52% of these participants were female.

The participants had an average age of 56, a mean BMI measurement of 38, and a mean HbA1c blood sugar level of slightly more than 8. They were studied at 68 medical facilities between January 2023 and May 2023.

In that study, researchers reported participants on semaglutide doses of 7.2 mg achieved an average weight loss of 13% compared to 10% for participants given 2.4 mg doses and close to 4% for those getting a placebo.

Researchers also reported that people on the 7.2 mg doses experienced more significant reductions in waist size and blood sugar levels.

In both studies, researchers said participants on the higher 7.2 mg doses reported some gastrointestinal side effects but that those health issues were manageable.

The scientists said further studies are warranted to determine long-term risks as well as benefits.

“These drugs are the most effective medication available at this time for weight loss. However, if someone meets the criteria for surgery, that is even more effective than the medications,” said Mir Ali, MD, a general surgeon, bariatric surgeon, and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in California.

“They result in significant weight loss and improvement in many health conditions related to obesity,” Ali told Healthline. “They do require long-term use as studies show a high incidence of weight regain if discontinued.”

Dan Azagury, MD, an associate professor of surgery and chief of the Section of Minimally Invasive and Bariatric Surgery at Stanford University in California, said the new studies are encouraging news.

“This new dosing of semaglutide offers a new more effective option for weight loss, compared to the current maximal dose,” he told Healthline. “Essentially more effective while maintaining a side effect profile that isn’t significantly worse for the typical [gastrointestinal] side effects that most patients experience.”

However, Azagury said there was one troubling side effect he saw in the research.

“The concern here at this new dose is the significant increase is dyseasthesia (which includes things like skin sensitivity, skin ‘pain’ or ‘burning sensation’),” he said. “This was significantly more frequent than the lower dose (22.9% vs. 6%).

“The upside of most side effects for these drugs is that they disappear when you discontinue,” Azagury added. “In this study, 18.7% (nearly 1 in 5) patients who had these issues still had not recovered by the end of the study (it is unclear how many of those had stopped the medication or not), so that is something that will require further studies to be better characterized.”

Ali noted that the recommended dose by the Food and Drug Administration (FDA) for a semaglutide drug is 2.4 mg taken weekly, so a higher dose would be outside those boundaries.

“These medications, like all medications do have side effects, some of which can be serious. If a patient is on a much higher dose, they have an increased risk for more significant side effects with long term use,” he said.

“Furthermore, this [higher dose] would be considered ‘off-label’ use of these medications, and they are already difficult to get coverage for through insurance, so there could be a significant out-of-pocket cost for the patient,” he added.

Ozempic and Rybelsus have been approved to treat type 2 diabetes. Wegovy is approved for use in weight management. Semaglutide drugs are available as both oral tablets and injections.

Another commonly used weight loss medication uses the active ingredient tirzepatide. Mounjaro is approved to treat type 2 diabetes. Zepbound is approved for use in weight management. These medications are available only as injections.

Previous studies have highlighted the effectiveness of these drugs in helping people lose weight.

Ali stressed that weight loss medications and surgery are simply tools to help someone in their weight loss journey.

He said if they don’t adopt a healthier lifestyle that includes a balanced diet, daily exercise, and adequate sleep, then they won’t be able to meet their weight loss goals.

“The goal of any weight loss intervention, whether it’s medications, surgery, or just counseling, is to provide tools to change to a healthier lifestyle and diet,” Ali explained. “If patients do not make these significant, long-term changes, then no intervention will remain effective for an extended period of time.”

“Weight loss drugs are most effective as part of a comprehensive management,” he said. “In our center, for example, patients prescribed these medications will also see our dietitians and be given access to resources and recommendations for diet change, exercise, etc. It is also important to have [a] follow-up to adapt treatment along the way.”