Research brief · 2026-09-09
Why Am I Still Hungry on a GLP-1?
GLP-1 receptor agonists such as semaglutide, liraglutide and tirzepatide are prescription medications, and one of their most consistent effects is a drop in appetite. Several trials have measured that directly rather than just tracking the scale. In a 2021 trial by Friedrichsen and colleagues in Diabetes, Obesity and Metabolism, 72 adults with obesity were given weekly semaglutide or placebo for 20 weeks. At a free-choice lunch, the semaglutide group ate about 35 percent less than the placebo group, and on validated questionnaires they reported less hunger, more fullness and fewer cravings. Body weight fell 9.9 percent versus 0.4 percent.
That is a large effect, but it is an average, and averages hide the people at the edges. A 2026 narrative review by Kuryłowicz and Czupryniak in the same journal searched for predictors of response and found that roughly one in ten participants in controlled obesity trials lost less than five percent of body weight, with real-world cohorts suggesting the share may be higher. Early genetic findings linking variation in the GLP-1 receptor gene to response were, in the authors' words, hypothesis-generating and unreplicated. Their conclusion was that no baseline characteristic currently predicts who will respond, and the best signal is simply how someone responds in the first weeks.
The more surprising finding concerns mechanism. The common explanation for GLP-1 appetite effects is that the drugs slow stomach emptying, so food sits longer and people feel full. The Friedrichsen trial measured gastric emptying directly and found no evidence of delay by week 20, despite the large drop in food intake. A 2026 secondary analysis by Friedman, Harmsen and Camilleri in Obesity tested the relationship in a 16-week liraglutide trial of 40 people and found gastric emptying speed accounted for only four to six percent of the variation in appetite. People whose stomachs emptied normally reported the same appetite suppression as those with delayed emptying.
That leaves most of the effect resting on something else, most likely signalling in appetite-regulating regions of the brain, where these drugs also act. The trials retrieved here ruled out the stomach as the main driver but did not isolate and measure the brain pathway directly.
The limits are clear. No test identifies in advance who will keep feeling hungry. The feeding studies ran 16 to 20 weeks, so whether appetite suppression holds over years, or what happens to hunger after stopping, was not tested. The controlled meal data come mainly from semaglutide and liraglutide, not tirzepatide. Anyone on one of these medications who feels it is not working should raise that with their physician rather than adjusting anything alone.
Sources
- Friedrichsen M, et al. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity
- Diabetes, Obesity and Metabolism 2021
- Friedman MI, Harmsen WS, Camilleri M. Appetite Suppression by GLP-1 Receptor Agonists: Role of Delayed Gastric Emptying
- Obesity (Silver Spring) 2026
- Kuryłowicz A, Czupryniak L. Responders Vs. Non-Responders or How to Predict the Response to GLP-1 or GLP-1/GIP Receptor Agonist Therapy
- Diabetes, Obesity and Metabolism 2026
Peptide Proof reports what studies found. We do not give medical advice, dosing guidance, or treatment recommendations.