NIH Research Identifies Cause of Weight-Loss Plateaus in Semaglutide Drugs

Brain Cell Response and Weight Plateaus

New research from the National Institutes of Health (NIH) has identified why weight loss often plateaus for patients using semaglutide, the active ingredient in medications such as Ozempic and Wegovy. The study reveals that semaglutide triggers different responses within the brain cells responsible for controlling appetite.

According to the NIH, these varying cellular responses provide insight into why the drugs do not produce the same weight-loss results for every individual. The findings suggest that the biological interaction between the drug and appetite-controlling neurons is a key factor in the efficacy and eventual stalling of weight loss.

Timing and Prevalence of Plateaus

Clinical data indicates that weight loss typically slows down after a specific period of treatment. Dr. Ali noted that studies show patients tend to reach a plateau with semaglutide at approximately 60 weeks. Other two-year trials involving people with obesity taking semaglutide showed an average weight loss of about 15%, which began to peter out just over a year after the initiation of the drug.

In comparison, the largest clinical trial for tirzepatide, another GLP-1 medication, found that participants reached a weight loss plateau at an average of 70 weeks. Additionally, the effectiveness of these drugs varies by patient profile; clinical trial data indicated that people with diabetes tended to lose weight less quickly and in smaller amounts than those without the condition, according to Dr. Hagan.

Nonresponders and Biological Resistance

Not all patients experience initial weight loss. Clinical trials funded by Novo Nordisk found that up to 23 percent of people fell into a "nonresponder" category, meaning they did not experience the expected weight loss from semaglutide.

Some medical perspectives attribute the plateau effect to the body's natural defense mechanisms. According to reports, the body may stop losing weight as quickly as it initially did because it attempts to retain extra weight as a defense against starvation.

Potential for Extended Efficacy

Researchers are currently investigating methods to extend the effects of GLP-1 drugs to help patients move past these plateaus. One such development involves the discovery of an enzyme called PapB.

This enzyme works by "tying off" peptide drugs, which scientists believe could make treatments like Ozempic and Wegovy work faster and last longer. This discovery is viewed as a potential way to "supercharge" diabetes and weight-loss treatments.