In this paper, we examine the long-term dynamics of obesity under conditions of treatment response and relapse using a four-compartment dynamical model motivated by the growing use of GLP-1 receptor agonist therapy. The model is partially calibrated to Georgia Behavioral Risk Factor Surveillance System (BRFSS) data from 2011 to 2024 and reproduces the observed trends closely. We establish the existence of a unique endemic equilibrium, linking model parameters directly to long-run prevalence. Simulations show that increasing the effective treatment-transition rate on its own produces only modest reductions in prevalence. Sensitivity analysis shows that, under the baseline setting, equilibrium obesity prevalence is most strongly influenced by obesity progression and partial recovery. Under the enhanced treatment-response setting, the effective treatment-transition rate becomes the strongest negative driver, while obesity progression remains the strongest positive driver and the influence of relapse increases substantially. Improving access to GLP-1-based treatment may increase the effective treatment-transition rate, but access alone is not sufficient. Lasting reductions in prevalence also require managing relapse, so policy design needs to address adherence and long-term retention, not access alone.
References
[1]
NCD Risk Factor Collaboration (NCD-RisC) (2024) Worldwide Trends in Underweight and Obesity from 1990 to 2022: A Pooled Analysis of 3663 Population-Representative Studies with 222 Million Children, Adolescents, and Adults. The Lancet, 403, 1027-1050. https://doi.org/10.1016/S0140-6736(23)02750-2
[2]
Ng, M., Gakidou, E., Lo, J., Abate, Y.H., Abbafati, C., Abbas, N., et al. (2025) Global, Regional, and National Prevalence of Adult Overweight and Obesity, 1990-2021, with Forecasts to 2050: A Forecasting Study for the Global Burden of Disease Study 2021. The Lancet, 405, 813-838. https://doi.org/10.1016/s0140-6736(25)00355-1
[3]
Emmerich, S.D., Fryar, C.D., Stierman, B. and Ogden, C.L. (2024) Obesity and Severe Obesity Prevalence in Adults: United States, August 2021-August 2023. NCHS Data Brief, 508, 1-8. https://doi.org/10.15620/cdc/159281
[4]
Centers for Disease Control and Prevention (2025) Adult Obesity Prevalence Maps, U.S. Department of Health and Human Services. https://www.cdc.gov/obesity/data-and-statistics/adult-obesity-prevalence-maps.html
[5]
Rubino, F., Cummings, D.E., Eckel, R.H., Cohen, R.V., Wilding, J.P.H., Brown, W.A., et al. (2025) Definition and Diagnostic Criteria of Clinical Obesity. The Lancet Diabetes & Endocrinology, 13, 221-262. https://doi.org/10.1016/s2213-8587(24)00316-4
[6]
Okunogbe, A., Nugent, R., Spencer, G., Powis, J., Ralston, J. and Wilding, J. (2022) Economic Impacts of Overweight and Obesity: Current and Future Estimates for 161 Countries. BMJ Global Health, 7, e009773. https://doi.org/10.1136/bmjgh-2022-009773
[7]
Wilding, J.P.H., Batterham, R.L., Calanna, S., Davies, M., Van Gaal, L.F., Lingvay, I., et al. (2021) Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 384, 989-1002. https://doi.org/10.1056/nejmoa2032183
[8]
Jastreboff, A.M., Aronne, L.J., Ahmad, N.N., Wharton, S., Connery, L., Alves, B., et al. (2022) Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 387, 205-216. https://doi.org/10.1056/nejmoa2206038
[9]
Jastreboff, A.M., Kaplan, L.M., Frías, J.P., Wu, Q., Du, Y., Gurbuz, S., et al. (2023) Triple-Hormone-Receptor Agonist Retatrutide for Obesity—A Phase 2 Trial. New England Journal of Medicine, 389, 514-526. https://doi.org/10.1056/nejmoa2301972
[10]
Rubino, D., Abrahamsson, N., Davies, M., Hesse, D., Greenway, F.L., Jensen, C., et al. (2021) Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults with Overweight or Obesity. JAMA, 325, 1414-1425. https://doi.org/10.1001/jama.2021.3224
[11]
Wilding, J.P.H., Batterham, R.L., Davies, M., Van Gaal, L.F., Kandler, K., Konakli, K., et al. (2022) Weight Regain and Cardiometabolic Effects after Withdrawal of Semaglutide: The Step 1 Trial Extension. Diabetes, Obesity and Metabolism, 24, 1553-1564. https://doi.org/10.1111/dom.14725
[12]
Aronne, L.J., Sattar, N., Horn, D.B., Bays, H.E., Wharton, S., Lin, W., et al. (2024) Continued Treatment with Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity. JAMA, 331, 38-48. https://doi.org/10.1001/jama.2023.24945
[13]
West, S., Scragg, J., Aveyard, P., Oke, J.L., Willis, L., Haffner, S.J.P., et al. (2026) Weight Regain after Cessation of Medication for Weight Management: Systematic Review and Meta-Analysis. BMJ, 392, e085304. https://doi.org/10.1136/bmj-2025-085304
[14]
Gleason, P.P., Urick, B.Y., Marshall, L.Z., Friedlander, N., Qiu, Y. and Leslie, R.S. (2024) Real-World Persistence and Adherence to Glucagon-Like Peptide-1 Receptor Agonists among Obese Commercially Insured Adults without Diabetes. Journal of Managed Care & Specialty Pharmacy, 30, 860-867. https://doi.org/10.18553/jmcp.2024.23332
[15]
Thomas, D.M., Weedermann, M., Fuemmeler, B.F., Martin, C.K., Dhurandhar, N.V., Bredlau, C., et al. (2014) Dynamic Model Predicting Overweight, Obesity, and Extreme Obesity Prevalence Trends. Obesity, 22, 590-597. https://doi.org/10.1002/oby.20520
[16]
Fallah-Fini, S., Rahmandad, H., Huang, T.T.-K., Bures, R.M. and Glass, T.A. (2014) Modeling US Adult Obesity Trends: A System Dynamics Model for Estimating Energy Imbalance Gap. American Journal of Public Health, 104, 1230-1239. https://doi.org/10.2105/ajph.2014.301882
[17]
Ejima, K., Aihara, K. and Nishiura, H. (2013) Modeling the Obesity Epidemic: Social Contagion and Its Implications for Control. Theoretical Biology and Medical Modelling, 10, Article 17. https://doi.org/10.1186/1742-4682-10-17
[18]
Lozano-Ochoa, E., Camacho, J.F. and Vargas-De-León, C. (2017) Qualitative Stability Analysis of an Obesity Epidemic Model with Social Contagion. Discrete Dynamics in Nature and Society, 2017, Article ID: 1084769. https://doi.org/10.1155/2017/1084769
[19]
Centers for Disease Control and Prevention (2026) Behavioral Risk Factor Surveillance System: Annual Survey Data. https://www.cdc.gov/brfss/annual_data/annual_data.htm
[20]
Centers for Disease Control and Prevention (2026) BRFSS Prevalence & Trends Data. https://www.cdc.gov/brfss/brfssprevalence/index.html
[21]
Jacquez, J.A. and Simon, C.P. (1993) Qualitative Theory of Compartmental Systems. SIAM Review, 35, 43-79. https://doi.org/10.1137/1035003
[22]
Pierannunzi, C., Town, M., Garvin, W., Shaw, F.E. and Balluz, L. (2012) Methodologic Changes in the Behavioral Risk Factor Surveillance System in 2011 and Potential Effects on Prevalence Estimates. Morbidity and Mortality Weekly Report, 61, 410-413.
[23]
Raue, A., Kreutz, C., Maiwald, T., Bachmann, J., Schilling, M., Klingmüller, U., et al. (2009) Structural and Practical Identifiability Analysis of Partially Observed Dynamical Models by Exploiting the Profile Likelihood. Bioinformatics, 25, 1923-1929. https://doi.org/10.1093/bioinformatics/btp358
[24]
Shampine, L.F. and Reichelt, M.W. (1997) The MATLAB ODE Suite. SIAM Journal on Scientific Computing, 18, 1-22. https://doi.org/10.1137/s1064827594276424
[25]
Centers for Medicare & Medicaid Services (2026) BALANCE Model: Better Approaches to Lifestyle and Nutrition for Comprehensive Health. https://www.cms.gov/priorities/innovation/innovation-models/balance
[26]
Podolsky, M.I., Raquib, R., Shafer, P.R., Hempstead, K., Ellis, R.P. and Stokes, A.C. (2025) Factors Associated with Semaglutide Initiation among Adults with Obesity. JAMA Network Open, 8, e2455222. https://doi.org/10.1001/jamanetworkopen.2024.55222
[27]
Hirsch, M.W. and Smith, H.L. (2006) Monotone Dynamical Systems. In: Ca?ada, A., Drábek, P. and Fonda, A., Eds., Handbook of Differential Equations: Ordinary Differential Equations, Vol. 2, Elsevier, 239-357. https://doi.org/10.1016/S1874-5725(05)80006-9
[28]
Mierczyński, J. (1987) Strictly Cooperative Systems with a First Integral. SIAM Journal on Mathematical Analysis, 18, 642-646. https://doi.org/10.1137/0518049