The powerful drop in hunger that some people experience when they begin semaglutide may become less noticeable over time. That does not necessarily mean the medication has stopped affecting how much they eat.
In a 60-week randomized trial, adults taking semaglutide continued to eat less during a laboratory lunch than those receiving a placebo. But by the later months of treatment, the two groups no longer reported clear differences in many measures of hunger, fullness and thoughts about food.
The study, published in the American Journal of Clinical Nutrition, was partly funded by Novo Nordisk, which makes the semaglutide weight-loss medication Wegovy. The company did not design, conduct, analyze or report the research. Several authors reported research funding, consulting work or advisory relationships with Novo Nordisk and other weight-loss companies.
“Many patients worry that their medication has stopped working if they notice some return of hunger after the first several months,” said lead author Jena S. Tronieri, a senior research investigator at the University of Pennsylvania’s Center for Weight and Eating Disorders. “Our findings show that even when people feel some of those sensations returning, semaglutide continues to help them eat less.”
Researchers enrolled 120 adults who had overweight or obesity but did not have type 2 diabetes. Participants were randomly assigned to receive a weekly 2.4-milligram dose of semaglutide or a placebo.
Everyone also received regular counseling focused on eating habits and physical activity.
At the beginning of the study and again after 20, 40 and 60 weeks, participants came to a laboratory for a five-hour visit. They ate the same breakfast and were later served lunch with instructions to eat until they felt comfortably full.
Researchers weighed the food before and after the meal to calculate how much each person ate.
At every follow-up visit, participants taking semaglutide ate fewer calories at lunch than those receiving the placebo. The difference was largest after 20 weeks, when the semaglutide group ate about 30% less.
The gap narrowed as the study continued, but it did not disappear. After 60 weeks, people taking semaglutide still ate about 22% less at the laboratory lunch than those receiving the placebo.
The results do not show that participants ate 22% fewer calories throughout every day. Researchers measured one controlled lunch at several points during the study, not everything participants ate at home, in restaurants or between meals.
Still, the laboratory meals offer a more direct measure than asking people to remember and report their own food intake.
Participants taking semaglutide lost an average of 15.1% of their starting weight after 60 weeks. Those receiving the placebo lost an average of 3.4%.
During the first 20 weeks, people taking semaglutide also reported less hunger, greater control over their eating and fewer persistent thoughts about food. These experiences are sometimes described collectively as reduced “food noise.”
By weeks 40 and 60, however, many of the reported differences between the semaglutide and placebo groups were no longer large enough to rule out chance.
That does not necessarily mean participants’ appetites returned completely to where they started. The study only shows that the difference between the two groups became less clear on the questionnaires researchers used.
It is also possible that people became accustomed to the medication’s effects, making the changes feel less dramatic than they did at the beginning. Semaglutide may also affect meal size in ways people do not consciously recognize.
“This study highlights an important distinction between people’s perceptions of their appetite and how they actually eat,” said Thomas A. Wadden, a professor of psychology in psychiatry and former director of the university’s Center for Weight and Eating Disorders.
The findings may be reassuring to people who notice more hunger after taking semaglutide for several months. But they do not provide a way for individuals to determine on their own whether a medication is still working.
Hunger can change for many reasons, and a person’s response to treatment cannot be judged from appetite alone. Anyone concerned about returning hunger, weight changes or side effects should discuss those changes with their prescriber rather than adjusting or stopping medication independently.
The study also cannot show how long the lower food intake would continue beyond 60 weeks. Nor did it test what happened after participants stopped taking semaglutide.
The results may not apply equally to everyone using the medication. Most participants were women, nearly three-quarters were white and 90% were non-Hispanic. People with type 2 diabetes were excluded.
More participants also left the placebo group before the study ended. Researchers used statistical methods to account for the missing information, but they could not know whether those participants would have changed the comparison between groups.
Side effects were common, particularly among those taking semaglutide. Nearly 94% of the semaglutide group reported gastrointestinal symptoms, compared with about 63% of the placebo group. These may have included problems such as nausea, vomiting, diarrhea or constipation.
Those symptoms could influence how much someone eats, although the study was not designed to separate the effects of side effects from the medication’s other effects on appetite and eating.
The findings help explain one part of semaglutide’s effect on weight. People taking the medication continued to eat less at a controlled meal, even after the early changes in hunger and food-related thoughts had become less distinct.
The study was partly supported by a Novo Nordisk investigator-sponsored research grant to the University of Pennsylvania. Novo Nordisk did not participate in the study’s design, conduct, analysis or reporting. Several authors reported research funding, consulting fees or advisory relationships with Novo Nordisk, Eli Lilly and other pharmaceutical or weight-management companies.