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The Ozempic Effect Outlasts the Feeling, New 60-Week Study Suggests
In A Nutshell
- Semaglutide users ate meaningfully fewer calories at controlled lab meals than a placebo group, and that gap held steady across 60 weeks of treatment.
- Self-reported hunger and food preoccupation improved most in the first 20 weeks, then leveled off to look similar to the placebo group by weeks 40 and 60.
- Actual eating behavior did not fade along with those feelings, semaglutide users kept eating roughly 240 to 292 fewer calories at test meals throughout the study.
- Nearly all participants on the drug reported at least one gastrointestinal adverse event, most commonly nausea, and three had serious adverse events including appendicitis and gallbladder removal.
People taking semaglutide, the active ingredient in Ozempic and Wegovy, often describe a strange new relationship with food: forgetting to eat, feeling full after a few bites, losing interest in meals they used to crave. Many also notice that feeling soften after a few months. Does that mean the drug has stopped working?
A new 60-week clinical trial from the University of Pennsylvania’s Center for Weight and Eating Disorders, published in The American Journal of Clinical Nutrition, suggests it doesn’t. Even as participants’ sense of reduced appetite eased over time, what they actually ate at controlled test meals barely budged, staying well below the placebo group’s for the entire study. Both groups also received the same lifestyle counseling, so the comparison reflects semaglutide added to that counseling, not semaglutide alone.
Semaglutide Cut Lab-Meal Calories by Roughly a Quarter for a Full Year
Researchers randomly assigned 120 adults with overweight or obesity to receive either semaglutide 2.4 mg or a placebo injection once a week for 60 weeks: 72 got the active drug, 48 got the placebo. Everyone also attended 17 counseling sessions on calorie goals and behavioral strategies.
To get an objective read on eating behavior, researchers brought participants into a lab at weeks 20, 40, and 60 for controlled meal tests. After a 12-hour overnight fast, each person ate a standardized 550-calorie breakfast. Four hours later, they were served a lunch with far more food than anyone could finish and told to eat until comfortably full. Researchers weighed every plate before and after, down to a tenth of a gram.
Participants also rated their hunger, fullness, and how often they thought about food. A computer task measured attraction to high-fat savory foods and showed no group difference at any point. A separate survey, the Power of Food Scale, measured how much the general food environment pulled at attention, and it did show a real difference between groups at weeks 20 and 40.
Appetite Ratings Faded While Eating Habits Held Steady
At week 20, the semaglutide group ate about 292 fewer calories at the lab lunch than the placebo group and reported far less hunger and food preoccupation over the previous week.
By weeks 40 and 60, the hunger and food-preoccupation gap closed. The semaglutide group and the placebo group reported roughly the same level of those feelings. Participants on the drug still felt better than at the study’s start, but they no longer stood out from the placebo group.
What people actually ate told a different story. The calorie gap barely moved: semaglutide participants ate about 240 fewer calories than placebo at week 40 and 270 fewer at week 60, both close to the week 20 gap of 292. Placebo participants, meanwhile, were eating about as much as they had at the start of the study by week 60, or slightly more, and their weight started creeping back up after week 40.
Body weight followed the eating pattern. Semaglutide participants lost an average of 9.9 kg by week 20, 15.0 kg by week 40, and held at a loss of 15.4 kg by week 60. Placebo participants lost considerably less and began regaining after week 40, finishing with an average loss of just 3.6 kg.
What Semaglutide Patients Should Know About Fading Hunger Cues
Researchers say the pattern carries a practical message for anyone on the drug long-term. A patient who no longer feels the strong appetite suppression from month one might assume the medication has quit working. The lab data argue otherwise. As the study authors put it, “patients could be counseled to expect a partial return of baseline appetite sensations after the first months of treatment, but, despite these changes, they will continue to eat less food.”
Nearly all participants reported at least one adverse event. Gastrointestinal issues were most common, in about 94% of the semaglutide group versus 63% on placebo, with nausea the leading complaint at 74% versus 25%. Three semaglutide participants had serious adverse events, including appendicitis, gallstones requiring gallbladder removal, and acute bronchitis. No serious events or deaths occurred in the placebo group.
Participants averaged 46 years old, weighed about 107 kg, and had a BMI of 37.5. About 78% were female, 72% White, and 90% non-Hispanic, demographics researchers say may limit how broadly findings apply elsewhere. The study also measured eating behavior at a single lab meal per visit rather than tracking daily food intake, and dropout ran higher in the placebo group, which researchers partly attributed to semaglutide’s commercial availability during the trial.
For a medication patients often take indefinitely, that’s a distinction worth remembering: what a patient feels at the dinner table and what actually ends up on their plate are not always the same measurement.
Disclaimer: This article summarizes findings from a peer-reviewed clinical trial for general informational purposes and is not a substitute for medical advice. Anyone taking or considering semaglutide should talk with their own doctor about their individual treatment and any changes in appetite or eating habits.
Paper Notes
Limitations
Researchers identified several important limitations. Dropout rates in the placebo group were significantly higher than expected, which the authors partly attributed to semaglutide’s commercial availability during the trial period, potentially drawing less satisfied placebo participants to seek treatment elsewhere. While researchers used a conservative statistical method to account for missing data, they acknowledged that the true impact of the missing placebo participants on the results cannot be known, and that missing data may have reduced the study’s ability to detect group differences. Additionally, the study only measured eating behavior during a single laboratory meal at each time point, which may not capture how people eat in their everyday lives, where food choice, timing, and environment play a larger role. Finally, the participant sample was predominantly female, White, and non-Hispanic, which limits how broadly the findings can be generalized to other populations.
Funding and Disclosures
This study was supported in part by an investigator-initiated research grant from Novo Nordisk, Inc. through its Investigator Sponsored Studies Program, awarded to the lead author on behalf of the University of Pennsylvania. Researchers stated that Novo Nordisk played no part in the design, conduct, analysis, or reporting of the study. Several authors disclosed financial relationships with pharmaceutical companies. The lead author reported receiving a grant from Novo Nordisk and consulting fees from Currax Pharmaceuticals. Another author reported grants from Novo Nordisk. A third author reported grants from multiple pharmaceutical companies and consulting fees from Novo Nordisk, AbbVie, Oxford Medical Products, and CVS CareMark. A senior author reported serving on advisory boards and receiving grants from Eli Lilly and Novo Nordisk. Authors declared that no generative AI tools were used in writing the manuscript.
Publication Details
Paper Title: Short- and long-term effects of semaglutide 2.4 mg on energy intake, appetite, and food reward: a 60-week, double-blind randomized controlled trial | Authors: Jena S. Tronieri, Kelly C. Allison, Katie DeRouen, Anastasia Amaro, Kayla G. Collins, Anokha Roy, Sanaiya Watts, Tasnia Ananna, Thomas A. Wadden | Institutions: Center for Weight and Eating Disorders, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Psychology, College of Arts and Sciences, East Carolina University, Greenville, NC; Penn Metabolic Medicine, Department of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA | Journal: The American Journal of Clinical Nutrition, Volume 124 (2026), Article 101403 | DOI: https://doi.org/10.1016/j.ajcnut.2026.101403 | Clinical Trial Registration: ClinicalTrials.gov, NCT05548647
