Semaglutide Helps People Eat Less Even as Hunger Returns

People taking semaglutide for weight loss continued to consume significantly fewer calories after 60 weeks on the medication, helping explain how the medication supports both initial weight loss and long-term weight maintenance. The study, published in the American Journal of Clinical Nutrition and led by investigators from Penn's Center for Weight and Eating Disorders and Penn Metabolic Medicine, is among the first to examine the long-term effects of semaglutide on eating behavior beyond the initial months of treatment.

Researchers found that while some of the medication's early reduction of hunger and food-related thoughts became less pronounced over time, participants continued to eat substantially fewer calories than those receiving placebo after more than a year of treatment.

"Many patients worry that their medication has stopped working if they notice some return of hunger after the first several months," said Jena S. Tronieri, PhD, lead author of the study and senior research investigator in the Center for Weight and Eating Disorders at Penn Medicine. "Our findings show that even when people feel some of those sensations returning, semaglutide continues to help them eat less. That sustained reduction in calorie intake appears to be a key reason why weight loss is maintained over time."

Measuring what people eat

The 60-week trial enrolled 120 adults who were overweight or had obesity. Participants received either a once-weekly 2.4 mg dose of semaglutide or placebo, along with regular lifestyle counseling focused on healthy eating and physical activity.

At the start of the study and again at weeks 20, 40, and 60, participants completed a five-hour laboratory assessment. After eating a standardized breakfast, they were offered lunch and told to eat until they felt comfortably full. Researchers carefully measured how many calories each participant consumed.

Compared with those receiving placebo, participants taking semaglutide consistently ate fewer calories throughout the study. Overall, semaglutide-treated participants consumed about 24 percent to 30 percent fewer calories than participants receiving placebo at the follow-up assessments through week 60.

Weight loss continued as calorie intake remained lower

Participants taking semaglutide achieved significant weight loss over the course of the study, with an average loss of 15.1 percent of initial body weight after 60 weeks of treatment. By comparison, participants receiving placebo lost an average of 3.4 percent of their body weight at week 60.

The study also explored participants' feelings of hunger, fullness, and food preoccupation (i.e., “food noise”). During the first 20 weeks, participants taking semaglutide reported less hunger, greater appetite control, and fewer thoughts about food. However, by weeks 40 and 60, the differences between the semaglutide and placebo groups on many of these subjective measures were no longer statistically significant.

"This study highlights an important distinction between people’s perceptions of their appetite and how they actually eat," said Thomas A. Wadden, PhD, a professor of Psychology in Psychiatry and former director of the Center for Weight and Eating Disorder. "People taking semaglutide for weight loss often notice dramatic reductions in hunger and food noise when they begin this treatment. If those sensations gradually become less noticeable, some may incorrectly assume the medication is no longer effective.”

"Our results suggest that patients may experience a partial return of appetite sensations over time, without losing the medication's benefit of continuing to reduce calorie intake, which is needed to maintain their new, lower body weight," Tronieri said. "Understanding that can help set realistic expectations and may encourage people to stay on treatment long term, as approved by the U.S. Food and Drug Administration and recommended by the treatment guidelines of numerous professional societies."