{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T20:32:19Z","timestamp":1786393939720,"version":"build-2736575974"},"reference-count":107,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Obesity, characterized by excess gain in body fat, alters energy balance and metabolic health. Weight loss is an effective strategy to favourably restore metabolic parameters in obese condition, and this can be achieved through caloric restriction, exercise, bariatric surgery and pharmacotherapy. Recently, glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) and associated combination therapies have proven to be effective weight loss inducers that also contribute to improvements in glycaemia and lipidaemia. However, side effects and socioeconomic barriers often lead to treatment discontinuation, which raises concerns about the effects of cessation on metabolic health. Regardless of the weight loss method, weight regain is common, although its underlying mechanisms remain unclear. Recent research has explored factors such as metabolic adaptation, shifts in appetite\u2010related hormones and changes in the adipose tissue to better understand these consequences. This review summarizes current knowledge on the metabolic and physiological responses to GLP\u20101RA\u2010induced weight loss and provides insight into potential mechanisms of weight regain after GLP\u20101RA withdrawal. It also explores how emerging GLP\u20101RA\u2010based combination therapies might help mitigate this challenge.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70753-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1113\/jp291081","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T20:00:12Z","timestamp":1786392012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adaptations of glucagon\u2010like peptide\u20101 receptor agonist\u2010induced weight loss, drivers of weight regain and future directions of therapeutics"],"prefix":"10.1113","author":[{"given":"Camille E. M.","family":"Piguet","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie","family":"Nucci","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1805-8844","authenticated-orcid":false,"given":"Jacqueline L.","family":"Beaudry","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"8","key":"e_1_2_2_2_1","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.2337\/db17-1385","article-title":"Liraglutide modulates appetite and body weight through glucagon\u2010like peptide 1 receptor\u2013Expressing glutamatergic neurons","volume":"67","author":"Adams J. M.","year":"2018","journal-title":"Diabetes"},{"issue":"1","key":"e_1_2_2_3_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/dom.70141","article-title":"Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study","volume":"28","author":"Alissou M.","year":"2026","journal-title":"Diabetes, Obesity & Metabolism"},{"issue":"2","key":"e_1_2_2_4_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jhep.2015.08.038","article-title":"Glucagon\u2010like peptide 1 decreases lipotoxicity in non\u2010alcoholic steatohepatitis","volume":"64","author":"Armstrong M. J.","year":"2016","journal-title":"Journal of Hepatology"},{"issue":"1","key":"e_1_2_2_5_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1056\/NEJMoa2416394","article-title":"Tirzepatide as compared with semaglutide for the treatment of obesity","volume":"393","author":"Aronne L. J.","year":"2025","journal-title":"New England Journal of Medicine"},{"issue":"1","key":"e_1_2_2_6_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1001\/jama.2023.24945","article-title":"Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity","volume":"331","author":"Aronne L. J.","year":"2024","journal-title":"Journal of the American Medical Association"},{"issue":"10546","key":"e_1_2_2_7_1","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1016\/S0140-6736(26)00967-0","article-title":"Efficacy and safety of retatrutide, a GIP, GLP\u20101, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND\u2010T2D\u20101): A double\u2010blind, randomised, phase 3 trial","volume":"407","author":"Bajaj H. S.","year":"2026","journal-title":"The Lancet"},{"issue":"11","key":"e_1_2_2_8_1","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1007\/s40618-025-02717-y","article-title":"Effects of 6\u2010month treatment with the GLP\u20101 receptor agonist liraglutide on 24\u2010hour energy metabolism and body composition in adults with obesity","volume":"48","author":"Basolo A.","year":"2025","journal-title":"Journal of Endocrinological Investigation"},{"issue":"10","key":"e_1_2_2_9_1","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.2337\/db14-0302","article-title":"GLP\u20101 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMPK","volume":"63","author":"Beiroa D.","year":"2014","journal-title":"Diabetes"},{"issue":"2","key":"e_1_2_2_10_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.2337\/dc22-1148","article-title":"GLP\u20101 receptor agonists and the risk of thyroid cancer","volume":"46","author":"Bezin J.","year":"2023","journal-title":"Diabetes Care"},{"key":"e_1_2_2_11_1","article-title":"Mechanisms of weight regain following weight loss","volume":"2013","author":"Blomain E. S.","year":"2013","journal-title":"International Scholarly Research Network Obesity"},{"key":"e_1_2_2_12_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/s00125-023-06053-9","article-title":"Dose\u2010response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon\/GLP\u20101 receptor agonist, compared with placebo and open\u2010label semaglutide in people with type 2 diabetes: A randomised clinical trial","volume":"67","author":"Bl\u00fcher M.","year":"2024","journal-title":"Diabetologia"},{"issue":"9","key":"e_1_2_2_13_1","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1111\/dom.12932","article-title":"Effects of once\u2010weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity","volume":"19","author":"Blundell J.","year":"2017","journal-title":"Diabetes, Obesity and Metabolism"},{"key":"e_1_2_2_14_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2026.103796","article-title":"Trajectory of weight regain after cessation of GLP\u20101 receptor agonists: A systematic review and nonlinear meta\u2010regression","volume":"93","author":"Budini B.","year":"2026","journal-title":"eClinicalMedicine"},{"key":"e_1_2_2_15_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ejim.2021.01.002","article-title":"Mechanisms of weight regain","volume":"93","author":"Busetto L.","year":"2021","journal-title":"European Journal of Internal Medicine"},{"issue":"6","key":"e_1_2_2_16_1","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/ijo.2013.162","article-title":"Effects of the once\u2010daily GLP\u20101 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non\u2010diabetic adults","volume":"38","author":"Can J.","year":"2014","journal-title":"International Journal of Obesity (2005)"},{"key":"e_1_2_2_17_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2025.107927","article-title":"Glucagon\u2010like peptide\u20101 receptor agonists and muscle mass effects","volume":"220","author":"Ceasovschih A.","year":"2025","journal-title":"Pharmacological Research"},{"issue":"1","key":"e_1_2_2_18_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1475-2891-13-13","article-title":"Is drop\u2010out from obesity treatment a predictable and preventable event?","volume":"13","author":"Colombo O.","year":"2014","journal-title":"Nutrition Journal"},{"issue":"2","key":"e_1_2_2_19_1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/oby.23633","article-title":"Glucagon\u2010like peptide\u20101\/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial","volume":"31","author":"Corbin K. D.","year":"2023","journal-title":"Obesity (Silver Spring)"},{"key":"e_1_2_2_20_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.molmet.2018.09.009","article-title":"LY3298176, a novel dual GIP and GLP\u20101 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept","volume":"18","author":"Coskun T.","year":"2018","journal-title":"Molecular Metabolism"},{"issue":"5","key":"e_1_2_2_21_1","article-title":"GLP\u20101 receptor agonist discontinuation among patients with obesity and\/or type 2 diabetes","volume":"7","author":"Do D.","year":"2024","journal-title":"Journal of the American Medical Association Network Open"},{"key":"e_1_2_2_22_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.626313","article-title":"Modulatory effect of intermittent fasting on adipose tissue inflammation: Amelioration of cardiovascular dysfunction in early metabolic impairment","volume":"12","author":"Dwaib H. S.","year":"2021","journal-title":"Frontiers in Pharmacology"},{"key":"e_1_2_2_23_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2025.102126","article-title":"Semaglutide and bariatric surgery induce distinct changes in the composition of mouse white adipose tissue","volume":"95","author":"Emont M. P.","year":"2025","journal-title":"Molecular Metabolism"},{"key":"e_1_2_2_24_1","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.numecd.2019.12.005","article-title":"Liraglutide decreases energy expenditure and does not affect the fat fraction of supraclavicular brown adipose tissue in patients with type 2 diabetes","volume":"30","author":"Eyk","year":"2020","journal-title":"Nutrition, Metabolism and Cardiovascular Diseases"},{"key":"e_1_2_2_25_1","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/s41430-024-01523-8","article-title":"Energy expenditure, metabolic adaptation, physical activity and energy intake following weight loss: Comparison between bariatric surgery and low\u2010calorie diet","volume":"79","author":"Falkenhain K.","year":"2025","journal-title":"European Journal of Clinical Nutrition"},{"issue":"3","key":"e_1_2_2_26_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1900\/RDS.2014.11.202","article-title":"Adverse effects of GLP\u20101 receptor agonists","volume":"11","author":"Filippatos T. D.","year":"2014","journal-title":"The Review of Diabetic Studies: RDS"},{"issue":"9","key":"e_1_2_2_27_1","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/s42255-020-0188-7","article-title":"Short\u2010chain fatty acids as potential regulators of skeletal muscle metabolism and function","volume":"2","author":"Frampton J.","year":"2020","journal-title":"Nature Metabolism"},{"issue":"6","key":"e_1_2_2_28_1","article-title":"Semaglutide lowers body weight in rodents via distributed neural pathways","volume":"5","author":"Gabery S.","year":"2020","journal-title":"Journal of Clinical Investigation Insight"},{"key":"e_1_2_2_29_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.lanepe.2025.101346","article-title":"Long\u2010term cancer risk in users of GLP\u20101 agonists in Denmark: A nationwide emulated trial","volume":"55","author":"Gamborg M.","year":"2025","journal-title":"The Lancet Regional Health \u2010 Europe"},{"issue":"3","key":"e_1_2_2_30_1","doi-asserted-by":"crossref","first-page":"E289","DOI":"10.1152\/ajpendo.00459.2024","article-title":"Quantitative interpretation and modeling of continuous nonprotein respiratory quotients","volume":"328","author":"Gan Z.","year":"2025","journal-title":"American Journal of Physiology\u2010Endocrinology and Metabolism"},{"issue":"7","key":"e_1_2_2_31_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1056\/NEJMoa2502081","article-title":"Coadministered cagrilintide and semaglutide in adults with overweight or obesity","volume":"393","author":"Garvey W. T.","year":"2025","journal-title":"New England Journal of Medicine"},{"issue":"1","key":"e_1_2_2_32_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40425-018-0371-5","article-title":"Dexamethasone\u2010induced immunosuppression: Mechanisms and implications for immunotherapy","volume":"6","author":"Giles A. J.","year":"2018","journal-title":"Journal for ImmunoTherapy of Cancer"},{"issue":"9","key":"e_1_2_2_33_1","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1002\/oby.23204","article-title":"Association of gastric emptying with postprandial appetite and satiety sensations in obesity","volume":"29","author":"Gonzalez\u2010Izundegui D.","year":"2021","journal-title":"Obesity (Silver Spring)"},{"key":"e_1_2_2_34_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.metabol.2019.154044","article-title":"Long acting GLP\u20101 analog liraglutide ameliorates skeletal muscle atrophy in rodents","volume":"103","author":"Gurjar A. A.","year":"2020","journal-title":"Metabolism"},{"issue":"9","key":"e_1_2_2_35_1","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1038\/sj.ijo.0803608","article-title":"How adaptations of substrate utilization regulate body composition","volume":"31","author":"Hall K. D.","year":"2007","journal-title":"International Journal of Obesity (2005)"},{"issue":"4","key":"e_1_2_2_36_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41574-022-00783-3","article-title":"Beyond the pancreas: Contrasting cardiometabolic actions of GIP and GLP1","volume":"19","author":"Hammoud R.","year":"2023","journal-title":"Nature Reviews Endocrinology"},{"issue":"8","key":"e_1_2_2_37_1","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.2337\/diacare.27.8.1915","article-title":"The effect of liraglutide, a long\u2010acting glucagon\u2010like peptide 1 derivative, on glycemic control, body composition, and 24\u2010h energy expenditure in patients with type 2 diabetes","volume":"27","author":"Harder H.","year":"2004","journal-title":"Diabetes Care"},{"issue":"1","key":"e_1_2_2_38_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/jdi.13315","article-title":"Glucagon regulates lipolysis and fatty acid oxidation through inositol triphosphate receptor 1 in the liver","volume":"12","author":"Hayashi Y.","year":"2021","journal-title":"Journal of Diabetes Investigation"},{"issue":"3","key":"e_1_2_2_39_1","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/s41591-026-04204-0","article-title":"Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: A randomized phase 2 trial","volume":"32","author":"Heymsfield S. B.","year":"2026","journal-title":"Nature Medicine"},{"issue":"8042","key":"e_1_2_2_40_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41586-024-08165-7","article-title":"Adipose tissue retains an epigenetic memory of obesity after weight loss","volume":"636","author":"Hinte L. C.","year":"2024","journal-title":"Nature"},{"issue":"1885","key":"e_1_2_2_41_1","doi-asserted-by":"crossref","DOI":"10.1098\/rstb.2022.0213","article-title":"Fat\u2010free mass and resting metabolic rate are determinants of energy intake: Implications for a theory of appetite control","volume":"378","author":"Hopkins M.","year":"2023","journal-title":"Philosophical Transactions of the Royal Society of London\u2010Series B: Biological Sciences"},{"issue":"10545","key":"e_1_2_2_42_1","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1016\/S0140-6736(26)00656-2","article-title":"Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT\u2010MAINTAIN): A multicentre, double\u2010blind, randomised, placebo\u2010controlled trial","volume":"407","author":"Horn D. B.","year":"2026","journal-title":"The Lancet"},{"issue":"2","key":"e_1_2_2_43_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.diabres.2012.02.016","article-title":"Effect of the once\u2010daily human GLP\u20101 analogue liraglutide on appetite, energy intake, energy expenditure and gastric emptying in type 2 diabetes","volume":"97","author":"Horowitz M.","year":"2012","journal-title":"Diabetes Research and Clinical Practice"},{"issue":"5","key":"e_1_2_2_44_1","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/ijo.2014.177","article-title":"Treatment with a GLP\u20101 receptor agonist diminishes the decrease in free plasma leptin during maintenance of weight loss","volume":"39","author":"Iepsen E. W.","year":"2015","journal-title":"International Journal of Obesity"},{"issue":"3","key":"e_1_2_2_45_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.14740\/jocmr3647","article-title":"Liraglutide reduces visceral and intrahepatic fat without significant loss of muscle mass in obese patients with type 2 diabetes: A prospective case series","volume":"11","author":"Ishii S.","year":"2019","journal-title":"Journal of Clinical Medicine Research"},{"issue":"3","key":"e_1_2_2_46_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide once weekly for the treatment of obesity","volume":"387","author":"Jastreboff A. M.","year":"2022","journal-title":"New England Journal of Medicine"},{"issue":"6","key":"e_1_2_2_47_1","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa2301972","article-title":"Triple\u2013Hormone\u2010receptor agonist retatrutide for obesity \u2014 A phase 2 trial","volume":"389","author":"Jastreboff A. M.","year":"2023","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_2_48_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP289449"},{"issue":"5","key":"e_1_2_2_49_1","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41366-025-01726-4","article-title":"Fasting appetite\u2010related gut hormone responses after weight loss induced by calorie restriction, exercise, or both in people with overweight or obesity: A meta\u2010analysis","volume":"49","author":"Jin Z.","year":"2025","journal-title":"International Journal of Obesity"},{"issue":"5","key":"e_1_2_2_50_1","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1210\/clinem\/dgz140","article-title":"GLP\u20101 analog modulates appetite, taste preference, gut hormones, and regional body fat stores in adults with obesity","volume":"105","author":"Kadouh H.","year":"2019","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_2_51_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.metabol.2024.156113","article-title":"Effect of glucagon\u2010like peptide\u20101 receptor agonists and co\u2010agonists on body composition: Systematic review and network meta\u2010analysis","volume":"164","author":"Karakasis P.","year":"2025","journal-title":"Metabolism"},{"issue":"15","key":"e_1_2_2_52_1","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1001\/jama.2018.14433","article-title":"Comparison of the performance of common measures of weight regain after bariatric surgery for association with clinical outcomes","volume":"320","author":"King W. C.","year":"2018","journal-title":"Journal of the American Medical Association"},{"key":"e_1_2_2_53_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.nsa.2023.103925","article-title":"GLP\u20101 receptor agonist semaglutide reduces appetite while increasing dopamine reward signaling","volume":"3","author":"Kooij K. L.","year":"2023","journal-title":"Neuroscience Applied"},{"issue":"3","key":"e_1_2_2_54_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.xcrm.2026.102665","article-title":"Weight loss with GLP\u20101 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans","volume":"7","author":"Langer H. T.","year":"2026","journal-title":"Cell Reports\u2010Medicine"},{"key":"e_1_2_2_55_1","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.2337\/db24-1071","article-title":"GLP\u20101\u2013Mediated targeting of inflammation corrects obesogenic memory in male mice","volume":"74","author":"L\u00e9on S.","year":"2025","journal-title":"Diabetes"},{"issue":"12","key":"e_1_2_2_56_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.clnu.2024.10.004","article-title":"Enteropancreatic hormone changes in caloric\u2010restricted diet interventions associate with post\u2010intervention weight maintenance","volume":"43","author":"Lin H.","year":"2024","journal-title":"Clinical Nutrition"},{"issue":"8115","key":"e_1_2_2_57_1","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41586-026-10427-5","article-title":"GLP\u20101R\u2013GIPR\u2013PPAR\u03b1\/\u03b3\/\u03b4 quintuple agonism corrects obesity and diabetes in mice","volume":"653","author":"Liskiewicz D.","year":"2026","journal-title":"Nature"},{"issue":"18","key":"e_1_2_2_58_1","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1056\/NEJMoa2028198","article-title":"Healthy weight loss maintenance with exercise, liraglutide, or both combined","volume":"384","author":"Lundgren J. R.","year":"2021","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_2_59_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.appet.2022.105965","article-title":"Creating the amylin story","volume":"172","author":"Lutz T. A.","year":"2022","journal-title":"Appetite"},{"issue":"6","key":"e_1_2_2_60_1","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/0031-9384(95)02067-5","article-title":"Amylin decreases meal size in rats","volume":"58","author":"Lutz T.","year":"1995","journal-title":"Physiology & Behavior"},{"issue":"1","key":"e_1_2_2_61_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/obr.12255","article-title":"The role for adipose tissue in weight regain after weight loss","volume":"16","author":"MacLean P. S.","year":"2015","journal-title":"Obesity Reviews"},{"issue":"4","key":"e_1_2_2_62_1","doi-asserted-by":"crossref","first-page":"928","DOI":"10.3945\/ajcn.116.146837","article-title":"Persistence of weight loss and acquired behaviors 2 y after stopping a 2\u2010y calorie restriction intervention12","volume":"105","author":"Marlatt K. L.","year":"2017","journal-title":"The American Journal of Clinical Nutrition"},{"issue":"7","key":"e_1_2_2_63_1","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1002\/oby.23450","article-title":"Metabolic adaptation after combined resistance and aerobic exercise training in older women","volume":"30","author":"Martins C.","year":"2022","journal-title":"Obesity (Silver Spring)"},{"issue":"6","key":"e_1_2_2_64_1","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.ajcnut.2023.10.010","article-title":"Metabolic adaptation is associated with a greater increase in appetite following weight loss: A longitudinal study","volume":"118","author":"Martins C.","year":"2023","journal-title":"The American Journal of Clinical Nutrition"},{"issue":"8","key":"e_1_2_2_65_1","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1002\/cbf.3751","article-title":"Semaglutide (GLP\u20101 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice","volume":"40","author":"Martins F. F.","year":"2022","journal-title":"Cell Biochemistry and Function"},{"issue":"1","key":"e_1_2_2_66_1","doi-asserted-by":"crossref","first-page":"4377","DOI":"10.1038\/s41467-025-59485-9","article-title":"GDF8 and activin A blockade protects against GLP\u20101\u2013induced muscle loss while enhancing fat loss in obese male mice and non\u2010human primates","volume":"16","author":"Mastaitis J. W.","year":"2025","journal-title":"Nature Communications"},{"key":"e_1_2_2_67_1","unstructured":"National Academies of Sciences Engineering and Medicine; Health and Medicine Division; Food and Nutrition Board; Committee on the Dietary Reference Intakes for Energy. Dietary Reference Intakes for Energy. Washington (DC): National Academies Press (US). (2023).Factors affecting energy expenditure and requirements. Available from:https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK591031\/"},{"issue":"9","key":"e_1_2_2_68_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S2213-8587(21)00179-0","article-title":"Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: A randomised, double\u2010blind, placebo\u2010controlled, clinical trial","volume":"9","author":"Neeland I. J.","year":"2021","journal-title":"The Lancet Diabetes & Endocrinology"},{"issue":"9","key":"e_1_2_2_69_1","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1519\/JSC.0000000000000924","article-title":"Repeatability of Respiratory exchange ratio time series analysis","volume":"29","author":"Nelson M. T.","year":"2015","journal-title":"The Journal of Strength & Conditioning Research"},{"issue":"3","key":"e_1_2_2_70_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s11892-023-01498-z","article-title":"Weight regain after bariatric surgery: Scope of the problem, causes, prevention, and treatment","volume":"23","author":"Noria S. F.","year":"2023","journal-title":"Current Diabetes Reports"},{"key":"e_1_2_2_71_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2024.101880","article-title":"Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP\u20101 receptor agonism","volume":"80","author":"Nunn E.","year":"2024","journal-title":"Molecular Metabolism"},{"key":"e_1_2_2_72_1","article-title":"Survodutide for the treatment of obesity","volume":"14","author":"Platz E.","year":"2026","journal-title":"Journal of the American College of Cardiology: Heart Failure"},{"issue":"5","key":"e_1_2_2_73_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1753-4887.1989.tb02817.x","article-title":"The impact of food intake and exercise on energy expenditure","volume":"47","author":"Poehlman E. T.","year":"1989","journal-title":"Nutrition Reviews"},{"issue":"11","key":"e_1_2_2_74_1","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1002\/oby.21653","article-title":"How strongly does appetite counter weight loss? Quantification of the feedback control of human energy intake","volume":"24","author":"Polidori D.","year":"2016","journal-title":"Obesity (Silver Spring)"},{"issue":"7","key":"e_1_2_2_75_1","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1210\/clinem\/dgac198","article-title":"Plasma levels of triglycerides and IL\u20106 are associated with weight regain and fat mass expansion","volume":"107","author":"Qiao Q.","year":"2022","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"e_1_2_2_76_1","doi-asserted-by":"crossref","DOI":"10.1177\/20420188251406456","article-title":"GLP\u20101 receptor agonists and gallbladder disease risk: Insights into molecular mechanisms and clinical implications","volume":"16","author":"Ram\u00edrez\u2010Mej\u00eda M. M.","year":"2025","journal-title":"Therapeutic Advances in Endocrinology and Metabolism"},{"issue":"12","key":"e_1_2_2_77_1","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1111\/dom.14516","article-title":"Liraglutide reduces cardiac adipose tissue in type 2 diabetes: A secondary analysis of the LIRAFLAME randomized placebo\u2010controlled trial","volume":"23","author":"Rasmussen I. K. B.","year":"2021","journal-title":"Diabetes, Obesity and Metabolism"},{"issue":"5","key":"e_1_2_2_78_1","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cmet.2025.03.011","article-title":"Tirzepatide did not impact metabolic adaptation in people with obesity, but increased fat oxidation","volume":"37","author":"Ravussin E.","year":"2025","journal-title":"Cell Metabolism"},{"issue":"3","key":"e_1_2_2_79_1","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.cmet.2024.11.006","article-title":"Unveiling adipose populations linked to metabolic health in obesity","volume":"37","author":"Reinisch I.","year":"2025","journal-title":"Cell Metabolism"},{"key":"e_1_2_2_80_1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2024.1386542","article-title":"Transforming body composition with semaglutide in adults with obesity and type 2 diabetes mellitus","volume":"15","author":"Rodr\u00edguez Jim\u00e9nez B.","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"e_1_2_2_81_1","article-title":"Discontinuation and reinitiation of dual\u2010labeled GLP\u20101 receptor agonists among US adults with overweight or obesity","volume":"8","author":"Rodriguez P. J.","year":"2025","journal-title":"Journal of the American Medical Association Network Open"},{"issue":"10549","key":"e_1_2_2_82_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0140-6736(26)01022-6","article-title":"Cagrilintide\u2013semaglutide (CagriSema) as an add\u2010on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): A randomised, double\u2010blind, placebo\u2010controlled, multicentre, phase 3 study","volume":"408","author":"Rosenstock J.","year":"2026","journal-title":"The Lancet"},{"key":"e_1_2_2_83_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/dom.70196","article-title":"Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double\u2010blind, placebo\u2010controlled, phase 3 trial (SYNCHRONIZETM\u20101)","volume":"28","author":"Roux C. W.","year":"2026","journal-title":"Diabetes, Obesity & Metabolism"},{"key":"e_1_2_2_84_1","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1001\/jama.2021.3224","article-title":"Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: The STEP 4 randomized clinical trial","volume":"325","author":"Rubino D.","year":"2021","journal-title":"Journal of the American Medical Association"},{"issue":"4","key":"e_1_2_2_85_1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/oby.70100","article-title":"Comparative efficacy of metabolic\/bariatric surgery versus GLP\u20101 receptor agonists: A network meta\u2010analysis of randomized controlled trials","volume":"34","author":"Sabatella L.","year":"2026","journal-title":"Obesity (Silver Spring)"},{"issue":"1","key":"e_1_2_2_86_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.4103\/aihb.aihb_106_22","article-title":"Obesity and overweight: A global public health issue","volume":"13","author":"Salam M. M.","year":"2023","journal-title":"Advances in Human Biology"},{"issue":"11","key":"e_1_2_2_87_1","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.2337\/dc17-0589","article-title":"Effects of liraglutide on weight loss, fat distribution, and \u03b2\u2010cell function in obese subjects with prediabetes or early type 2 diabetes","volume":"40","author":"Santilli F.","year":"2017","journal-title":"Diabetes Care"},{"issue":"1","key":"e_1_2_2_88_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/oby.23596","article-title":"Marked weight loss on liraglutide 3.0 mg: Real\u2010life experience of a Swiss cohort with obesity","volume":"31","author":"Santini S.","year":"2023","journal-title":"Obesity"},{"key":"e_1_2_2_89_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2147\/DMSO.S141235","article-title":"Reasons for discontinuation of GLP1 receptor agonists: Data from a real\u2010world cross\u2010sectional survey of physicians and their patients with type 2 diabetes","volume":"10","author":"Sikirica M. V.","year":"2017","journal-title":"Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy"},{"issue":"6","key":"e_1_2_2_90_1","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1172\/JCI72434","article-title":"Neuronal GLP1R mediates liraglutide's anorectic but not glucose\u2010lowering effect","volume":"124","author":"Sisley S.","year":"2014","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_2_91_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.peptides.2025.171367","article-title":"The role of leptin and ghrelin in the regulation of appetite in obesity","volume":"186","author":"Skoracka K.","year":"2025","journal-title":"Peptides"},{"issue":"1","key":"e_1_2_2_92_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1089\/dia.2014.0188","article-title":"Gastrointestinal adverse events of glucagon\u2010like peptide\u20101 receptor agonists in patients with type 2 diabetes: A systematic review and network meta\u2010analysis","volume":"17","author":"Sun F.","year":"2015","journal-title":"Diabetes Technology & Therapeutics"},{"issue":"7","key":"e_1_2_2_93_1","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.cmet.2025.04.018","article-title":"Semaglutide effects on energy balance are mediated by Adcyap1+ neurons in the dorsal vagal complex","volume":"37","author":"Teixidor\u2010Deulofeu J.","year":"2025","journal-title":"Cell Metabolism"},{"issue":"4","key":"e_1_2_2_94_1","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/2231-4040.90879","article-title":"The peroxisome proliferator\u2010activated receptor: A family of nuclear receptors role in various diseases","volume":"2","author":"Tyagi S.","year":"2011","journal-title":"Journal of Advanced Pharmaceutical Technology & Research"},{"issue":"7","key":"e_1_2_2_95_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.14740\/jocmr4987","article-title":"Oral semaglutide induces loss of body fat mass without affecting muscle mass in patients with type 2 diabetes","volume":"15","author":"Uchiyama S.","year":"2023","journal-title":"Journal of Clinical Medicine Research"},{"issue":"2","key":"e_1_2_2_96_1","doi-asserted-by":"crossref","DOI":"10.1161\/HYPERTENSIONAHA.125.26055","article-title":"CagriSema reduces blood pressure in adults with overweight or obesity: REDEFINE 1","volume":"83","author":"Verma S.","year":"2026","journal-title":"Hypertension"},{"issue":"1","key":"e_1_2_2_97_1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s13098-024-01501-x","article-title":"Effect of survodutide, a glucagon and GLP\u20101 receptor dual agonist, on weight loss: A meta\u2010analysis of randomized controlled trials","volume":"16","author":"Wan H.","year":"2024","journal-title":"Diabetology & Metabolic Syndrome"},{"issue":"3","key":"e_1_2_2_98_1","doi-asserted-by":"crossref","first-page":"E356","DOI":"10.1152\/ajpendo.00530.2025","article-title":"Substrate utilization during short\u2010term fasting in older men and women","volume":"330","author":"Wang S. Y.","year":"2026","journal-title":"American Journal of Physiology\u2010 Endocrinology and Metabolism"},{"issue":"1","key":"e_1_2_2_99_1","article-title":"Real\u2010world weight change, adherence, and discontinuation among patients with type 2 diabetes initiating glucagon\u2010like peptide\u20101 receptor agonists in the UK","volume":"10","author":"Weiss T.","year":"2022","journal-title":"British Medical Journal Open Diabetes"},{"issue":"2","key":"e_1_2_2_100_1","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1111\/dom.70263","article-title":"Baseline characteristics in the SYNCHRONIZETM\u20102 randomized phase 3 trial of survodutide, a glucagon receptor\/GLP\u20101 receptor dual agonist, for obesity in people with type 2 diabetes","volume":"28","author":"Wharton S.","year":"2026","journal-title":"Diabetes, Obesity & Metabolism"},{"issue":"8","key":"e_1_2_2_101_1","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1038\/s41366-022-01150-y","article-title":"A higher proportion of small adipocytes is associated with increased visceral and ectopic lipid accumulation during weight gain in response to overfeeding in men","volume":"46","author":"White U.","year":"2022","journal-title":"International Journal of Obesity (2005)"},{"issue":"1","key":"e_1_2_2_102_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.physbeh.2010.04.012","article-title":"Central amylin acts as an adiposity signal to control body weight and energy expenditure","volume":"101","author":"Wielinga P. Y.","year":"2010","journal-title":"Physiology & Behavior"},{"issue":"8","key":"e_1_2_2_103_1","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1111\/dom.14725","article-title":"Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension","volume":"24","author":"Wilding J. P. H.","year":"2022","journal-title":"Diabetes, Obesity & Metabolism"},{"issue":"1","key":"e_1_2_2_104_1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s12020-024-03734-2","article-title":"Liraglutide induced browning of visceral white adipose through regulation of miRNAs in high\u2010fat\u2010diet\u2010induced obese mice","volume":"85","author":"Zhao L.","year":"2024","journal-title":"Endocrine"},{"issue":"2","key":"e_1_2_2_105_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1530\/JOE-18-0374","article-title":"The key role of a glucagon\u2010like peptide\u20101 receptor agonist in body fat redistribution","volume":"240","author":"Zhao L.","year":"2019","journal-title":"Journal of Endocrinology"},{"issue":"1","key":"e_1_2_2_106_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41392-024-01931-z","article-title":"Glucagon\u2010like peptide\u20101 receptor: Mechanisms and advances in therapy","volume":"9","author":"Zheng Z.","year":"2024","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"e_1_2_2_107_1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1095432","article-title":"Proteomic analysis reveals semaglutide impacts lipogenic protein expression in epididymal adipose tissue of obese mice","volume":"14","author":"Zhu R.","year":"2023","journal-title":"Frontiers in Endocrinology"},{"issue":"6","key":"e_1_2_2_108_1","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/cmi.2017.36","article-title":"CD4+ T cells memorize obesity and promote weight regain","volume":"15","author":"Zou J.","year":"2018","journal-title":"Cellular & Molecular Immunology"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP291081","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP291081","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP291081","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T20:00:25Z","timestamp":1786392025000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP291081"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":107,"alternative-id":["10.1113\/JP291081"],"URL":"https:\/\/doi.org\/10.1113\/jp291081","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"assertion":[{"value":"2026-02-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"JP291081"}}