How strongly does appetite counter weight loss? Quantification of the feedback control of human energy intake
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Abstract
Objective: To quantify the feedback control of energy intake in response to long‐term covert manipulation of energy balance in free‐living humans. Methods: A validated mathematical method was used to calculate energy intake changes during a 52‐week placebo‐controlled trial in 153 patients treated with canagliflozin, a sodium glucose co‐transporter inhibitor that increases urinary glucose excretion, thereby resulting in weight loss without patients being directly aware of the energy deficit. The relationship between the body weight time course and the calculated energy intake changes was analyzed using principles from engineering control theory. Results: It was discovered that weight loss leads to a proportional increase in appetite resulting in eating above baseline by ∼100 kcal/day per kilogram of lost weight—an amount more than threefold larger than the corresponding energy expenditure adaptations. Conclusions: While energy expenditure adaptations have often been considered the main reason for slowing of weight loss and subsequent regain, feedback control of energy intake plays an even larger role and helps explain why long‐term maintenance of a reduced body weight is so difficult.
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Weight loss causes persistent endocrine adaptations that raise appetite and lower satiety, opposing further loss and long-term maintenance.
“Weight loss is accompanied by persistent endocrine adaptations30 that increase appetite and decrease satiety31 thereby resisting continued weight loss and conspiring against long-term weight maintenance.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
The Discussion (page not available) reports that weight loss increases appetite and makes long-term maintenance difficult; it also says this pattern is consistent with changes in appetite-regulating hormones. The paper does not report a decrease in satiety or establish that endocrine adaptations cause the increased appetite. In the citing sentence, the separate citation 30 is attached to the endocrine-adaptations phrase. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn the model, the simulated patient who plateaued at six months and then regained maintained more than about 70% of initial intervention effort until the plateau.
“For example, the model-calculated intervention effort for the simulated patient who experiences the weight plateau at six months followed by weight regain (Figure 2, blue curves) maintains more than ~70% of their initial intervention effort until the plateau.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
The Results describe a weight-loss plateau after 6–8 months followed by regain, and identify Figure 3C as an index of ongoing intervention effort. The Discussion also describes persistent effort over the first six months. Our copy does not state that effort remained above approximately 70% of its initial level; its Figure 2 concerns feedback control during canagliflozin treatment, not the plateau-and-regain example. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn the model, both example women had rapid weight and fat loss after large initial calorie intake reductions, with a modest decrease in calorie expenditure that slowed weight loss.
“In both women, large decreases in calorie intake at the start of the intervention result in rapid loss of weight and body fat leading to a modest decrease in calorie expenditure that contributes to slowing weight loss.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
The Results (page unavailable) describe a large initial reduction in energy intake, weight loss, and relatively minor changes in energy expenditure. The paper presents an average weight trajectory, not two example women, and these passages do not establish their body-fat loss. The Results and Discussion attribute the weight-loss plateau chiefly to intake returning toward baseline, rather than to the modest expenditure decrease. (LLM, conf=0.87)
Experimental — accuracy not yet measuredFrom a calorie balance perspective, a patient who maintains lost weight after the first year may eat only about 100 kcal/d less than one who regains long-term.
“From a purely calorie balance perspective, a patient who maintains lost weight after the first year of an intervention (Figure 2, orange curves) may be eating only about 100 kcal/d fewer than a patient who experiences long-term weight regain (Figure 2, blue curves).”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
The Results (page unavailable) describe a weight-loss trajectory followed by slow regain: intake was within 100 kcal/day of baseline at the eight-month plateau and practically at baseline after one year. They do not compare patients who maintain weight loss after year one with patients who regain it, or establish a 100 kcal/day difference between those groups. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPreventing weight regain requires about 300-500 kcal/d of increased persistent effort to counter slowing metabolism and increased appetite after weight loss.
“However, such a small difference in food intake behavior is somewhat misleading considering that prevention of weight regain requires about 300–500 kcal/d of increased persistent effort to counter the ongoing slowing of metabolism and increased appetite associated with the lost weight.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
The Results describe persistent effort to resist increased appetite, and the Discussion says maintaining weight loss involves both increased appetite and suppressed energy expenditure. The paper estimates an appetite increase of about 100 kcal/day per kilogram lost, but does not state that preventing weight regain generally requires 300–500 kcal/day of effort; that amount depends on how much weight was lost. Page numbers were unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
The study used a validated mathematical model of human energy balance dynamics to simulate weight loss trajectories.
“Using a validated mathematical model of human energy balance dynamics27,31, Figure 2 illustrates the energy balance dynamics underlying the weight loss time courses of two example 90 kg women who either regain (blue curves) or maintain (orange curves) much of their lost weight after reaching a plateau within the first year of a diet intervention.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
Avoiding overeating to match increased appetite requires relatively persistent effort that grows with weight lost.
“Furthermore, a relatively persistent effort is required to avoid overeating to match the increased appetite that grows in proportion to the weight lost31.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
In the model, the exponential rise in calorie intake from its initially reduced level was the main factor stopping weight loss within the first year.
“However, the exponential rise in calorie intake from its initially reduced value is the primary factor that halts weight loss within the first year.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
For each kilogram of weight lost, calorie expenditure falls by about 20-30 kcal/day while appetite rises by about 100 kcal/day above pre-weight-loss baseline.
“Specifically, it has been estimated that for each kilogram of lost weight, calorie expenditure decreases by about 20–30 kcal/d whereas appetite increases by about 100 kcal/d above the baseline level prior to weight loss31.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
At the model weight plateau, calorie expenditure was less than 200 kcal/d below baseline, while appetite had risen by 400-600 kcal/d and energy intake by 600-700 kcal/d since intervention start.
“In contrast to the modest drop in calorie expenditure of less than 200 kcal/d at the weight plateau, appetite has risen by 400–600 kcal/d and energy intake has increased by 600–700 kcal/d since the start of the intervention.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [31]
The mechanisms behind weight regain seem to comprise biological reactions to weight loss, including decreases in resting and non-resting energy expenditure beyond what can be expected based on the actual loss of body mass and changes in appetite-regulating hormones favoring increased food intake.
“The mechanisms behind the weight regain seem to comprise biological reactions to weight loss, including decreases in resting and non-resting energy expenditure beyond what can be expected based on the actual loss of body mass2,3 along with changes in appetite-regulating hormones favoring increased food intake4–6.”
Increased appetite promotes increased energy intake and weight regain.
“Increased appetite promotes increased energy intake and weight regain4,31, and is therefore likely to have contributed to a positive energy balance and thereby the weight regain of almost 50% of the initial weight loss within one year observed in the placebo group.”
A mathematical model of energy balance in individuals with overweight and obesity showed that appetite increased by approximately 100 kcal/day for each kg of body weight lost.
“A mathematical model of energy balance in a study of individuals with overweight and obesity showed that appetite increased by approximately 100 kcal/day for each kg of body weight lost [65].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [65]
Mathematical models have estimated that for every kilogram of body weight lost, appetite increases by approximately 100 kcal per day.
“Mathematical models have estimated that for every kilogram of body weight lost, appetite increases by approximately 100 kcal per day [65].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [65]
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Żurawski, T., & Bartosiewicz, A. (2025) · Nutrients · doi:10.3390/nu18010012 · Cited by 18 · see citing works
Zhu, R., Fogelholm, M., Larsen, T. M., Poppitt, S. D., Silvestre, M. P., Vestentoft, P. S., Jalo, E., Navas-Carretero, S., Huttunen-Lenz, M., Taylor, M. A., et al. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.685648 · Cited by 16 · see citing works
Oral, A., Küçük, C., & Köse, M. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13206121 · Cited by 8 · see citing works
- Authors
- Polidori, D., Sanghvi, A., Seeley, R. J., & Hall, K. D.
- Affiliations
- Janssen Research & Development, LLC San Diego California USA
- National Institutes of Health (US)
- University of Michigan (US)
- Corresponding author
- Hall, Kevin D.
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2016-11
- Volume
- 24
- Issue
- 11
- Pages
- 2289-2295
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- PMC
- PMC5108589
- OpenAlex
- W2547272800
- Semantic Scholar
- 513a21883d37cc4cf5299374f9e2ce37d74ff8fb
- Cited by
- 209
- References
- 43
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 30 · 2023: 16 · 2022: 20 · 2021: 29 · 2020: 25 · 2019: 19 · 2018: 20 · 2017: 19 · 2016: 1 · 2014: 1
- FWCI
- 12.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Obesity (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health
- Janssen Research and Development
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- appetite, energy intake, feedback control, weight loss, canagliflozin, SGLT2 inhibitors, energy balance, weight regain, weight maintenance, control theory, urinary glucose excretion
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Adult, Aged, Appetite, Body Weight, Energy Intake, Diabetes Mellitus, Type 2, Energy Metabolism, Female, Glucose, Humans, Hypoglycemic Agents, Male, Middle Aged, Models, Theoretical, Reproducibility of Results, Biomarkers, Weight Loss, Body Mass Index, Feedback, Physiological, Sodium-Glucose Transporter 2, Waist Circumference
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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