A 60-week study published in the American Journal of Clinical Nutrition found that people taking semaglutide for weight loss continued to consume 24% to 30% fewer calories than those on placebo, even as subjective feelings of hunger and food noise partially returned. The researchers from Penn…
A new study published in the American Journal of Clinical Nutrition provides evidence that semaglutide helps people consume significantly fewer calories even after more than a year of treatment. The research, 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 therapy.
The 60-week trial enrolled 120 adults who had overweight or obesity. Participants received either a once-weekly 2.4 mg dose of semaglutide or a placebo, along with regular lifestyle counseling focused on healthy eating and physical activity. The study aimed to understand how the medication supports both initial weight loss and long-term weight maintenance.
At the start of the study and again at weeks 20, 40, and 60, participants completed a five-hour laboratory assessment. During these sessions, they ate a standardized breakfast and were later offered lunch with instructions to eat until they felt comfortably full. Researchers carefully measured the number of calories each participant consumed.
Throughout the study, participants taking semaglutide consistently ate fewer calories compared to those receiving placebo. At the follow-up assessments through week 60, semaglutide-treated participants consumed about 24% to 30% fewer calories than participants in the placebo group. This sustained reduction in calorie intake is a key reason why weight loss is maintained over time, according to the researchers.
Participants taking semaglutide achieved significant weight loss over the course of the study. After 60 weeks of treatment, they lost an average of 15.1 percent of their initial body weight. By comparison, participants receiving placebo lost an average of 3.4 percent of their body weight at week 60. These results underscore the medication's effectiveness in promoting and maintaining weight loss.
"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."
The study also explored participants' subjective experiences of hunger, fullness, and food preoccupation, often referred to as "food noise." During the first 20 weeks, participants taking semaglutide reported less hunger, greater appetite control, and fewer thoughts about food compared to those on placebo. 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 finding suggests that while the medication's early reduction of hunger and food-related thoughts may become less pronounced over time, the actual impact on eating behavior persists. Thomas A. Wadden, PhD, professor of Psychology in Psychiatry and the former director of the Center for Weight and Eating Disorders, commented on this distinction. "This study highlights an important distinction between people's perceptions of their appetite and how they actually eat," Wadden said. "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."
The research provides actionable insights for patients and healthcare providers regarding realistic expectations during semaglutide therapy. The partial return of appetite sensations does not signal a loss of the medication's benefit in reducing calorie intake, which is crucial for maintaining a new, lower body weight. Tronieri emphasized that understanding this can encourage patients to remain on treatment long-term.
"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 US Food and Drug Administration and recommended by the treatment guidelines of numerous professional societies."
Penn Medicine, where the study was conducted, is one of the world's leading academic medical centers. It is dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn's Raymond and Ruth Perelman School of Medicine, which was founded in 1765 as the nation's first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with more than $588 million awarded in the 2024 fiscal year. Home to a proud history of firsts, Penn Medicine teams have pioneered discoveries that have shaped modern medicine, including CAR T cell therapy for cancer and the Nobel Prize-winning mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System cares for patients in facilities and their homes stretching from the Susquehanna River in Pennsylvania to the New Jersey shore. UPHS facilities include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Doylestown Health, Lancaster General Health, Princeton Health, and Pennsylvania Hospital, which was the nation's first hospital, chartered in 1751. Additional facilities and enterprises include Penn Medicine at Home, GSPP Rehabilitation, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is a $13.7 billion enterprise powered by more than 50,000 talented faculty and staff. The study's findings add to the growing body of evidence supporting semaglutide's role in weight management and highlight the importance of continued treatment for sustained benefits.
Peptides referenced: Semaglutide.
Related reading: Mounjaro vs. Semaglutide: Understanding the Key Differences, Semaglutide vs Liraglutide Study Reveals Diabetes Risk Difference, FDA Approves First Oral PCSK9 Inhibitor Lipfendra from Merck, FDA Issues Warnings to 25 Firms Over Compounded GLP-1 Claims.