Semaglutide 2.4 mg Sustains Energy Intake Reduction for 60 Weeks Despite Declining Subjective Appetite Benefits
Background
Achieving and maintaining long-term weight loss in individuals with overweight and obesity remains a significant challenge, often limited by compensatory mechanisms that increase appetite and food intake. While GLP-1 receptor agonists like semaglutide have shown efficacy in short-term weight reduction, understanding their sustained impact on eating behaviors is crucial for long-term success. Previous studies, typically up to 20 weeks, demonstrated initial reductions in energy intake, appetite, and food reward, but lacked the duration to assess whether these effects persist to support weight maintenance.
Study Design
This 60-week, double-blind, randomized controlled trial enrolled 120 adults with overweight/obesity, assigning them in a 3:2 ratio to either semaglutide 2.4 mg once weekly or placebo. Participants underwent laboratory assessments at weeks 0, 20, 40, and 60. Primary endpoints included ad libitum energy intake during a standardized lunch, measured after a 4-hour post-breakfast period. Subjective appetite ratings (fasting and post-breakfast) and food reward measures, including the Power of Food Scale, were also collected. Data analysis used ANCOVAs controlling for baseline values.
Results
The semaglutide group demonstrated significantly greater reductions in ad libitum energy intake compared to placebo at all measured time points. At week 20, participants consumed a mean of 294.6±64.0 kcal less; at week 40, 250.1±94.4 kcal less; and at week 60, 238.3±92.5 kcal less. These sustained reductions highlight a persistent effect on caloric consumption. While subjective appetite suppression following breakfast significantly increased at week 20 (MD=2197±823) and past-week hunger (MD=-17.4±4.8) and food preoccupation (MD=-14.9±4.5) significantly decreased at week 20, these differences were not significant at weeks 40 or 60. However, responsiveness to food, a measure of food reward, was significantly reduced in the semaglutide group at week 20 (MD=-0.4±0.2) and week 40 (MD=-0.6±0.2).
Key Findings
- Semaglutide 2.4 mg reduced
ad libitum energy intakeby 294.6 kcal at week 20 vs. placebo. - Energy intake remained significantly reduced by 250.1 kcal at week 40 and 238.3 kcal at week 60.
- Subjective appetite suppression, hunger, and food preoccupation improved significantly at week 20.
- Subjective appetite benefits were no longer significantly different from placebo at weeks 40 and 60.
- Responsiveness to food (food reward) was significantly reduced at weeks 20 and 40.
Why It Matters
This study provides critical evidence that semaglutide 2.4 mg sustains objective reductions in caloric intake over 60 weeks, a key mechanism for long-term weight management, even if subjective feelings of appetite suppression become less pronounced over time. For individuals using or considering GLP-1 receptor agonists for weight loss, this suggests that the medication's efficacy extends beyond initial appetite changes, potentially by altering fundamental metabolic or neurological pathways related to food consumption. The consistent reduction in energy intake, despite waning subjective appetite benefits, indicates a robust, long-term impact on eating behavior that supports sustained weight loss and maintenance. This finding reinforces the value of semaglutide as a long-term therapeutic option for obesity.
semaglutide
obesity
weight-loss
energy-intake
appetite
food-reward