Higher doses of GLP-1s are not ideal for long-term use

Experts not involved in the new studies say GLP-1 weight loss drugs and bariatric surgery can be highly effective in helping people manage their weight.

“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.