The science of obesity
DOI:
https://doi.org/10.7196/SAMJ.2025.v115i9b.3600Keywords:
Obesity, Science, GuidelineAbstract
KEY MESSAGES
• Obesity arises from a complex interplay of genetic, biological, behavioural, psychosocial and environmental factors.
• Obesity has a strong genetic component, with twin studies indicating a 50 - 80% concordance in body mass index (BMI) and regional fat distribution. A Swedish study on identical twins raised apart found no correlation between BMI and their adoptive families but a strong correlation with their biological twin, despite being raised in separate households.
• The regulation of appetite, body weight and energy balance is highly complex, governed by a network of hormonal signals from the gut, adipose tissue and other organs, as well as neural signals that shape eating behaviours. Many of these signalling pathways are disrupted in people living with obesity.
• Since body weight is homeostatically regulated, weight loss triggers physiological adaptations that promote weight regain. These include a decrease in energy expenditure, and hormonal changes that enhance appetite while reducing satiety.
• Adipose tissue influences the central regulation of energy homeostasis, and excess adiposity can become dysfunctional, with production of proinflammatory cytokines and associated metabolic health complications.
• Individual variations in body composition, fat distribution and function result in a highly variable threshold at which excess adiposity begins to negatively affect health.
• Emerging research in obesity science has widened to include brown fat, the gut microbiome, immune system regulation, and the intricate mechanisms that regulate body weight.
• Obesity can be classified as primary, secondary and genetic obesity.
• In the current management of primary obesity, prevention (the path in) and treatment (the path out) need to be distinctly separated.
• Effective primary obesity treatment requires an integrated approach that addresses the non-modifiable cause (increased appetite) together with modifiable contributors (poor diet quality, increased stress, poor sleep, reduced physical activity and increased sedentary behaviour). Behavioural modification and psychological support provide additional benefit.
• Effective treatment in genetic and secondary obesity requires treatment of the underlying causes along with modification of the contributors.
References
1. ASOI Adult Obesity Clinical Practice Guideline adaptation (ASOI version 1, 2022) by: Finucane F, Dunlevy C, Hogan A, Roche HM, O’Shea D. Chapter adapted from: Lau D, Wharton S. https://asoi. info/guidelines/science/ (accessed 10 April 2025).
2. Bluher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract Res Clin Endocrinol Metab 2013;27(2):163-177. https://doi.org/10.1016/j.beem.2013.02.005
3. Rubino F, Cummings DE, Eckel RH, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol 2025;13(3):221-262. https://doi.org/10.1016/S2213-8587(24)00316-4
4. Hill JO. Understanding and addressing the epidemic of obesity: An energy balance perspective. Endocr Rev 2006;27(7):750-761. https://doi.org/10.1210/er.2006-0032
5. Swinburn BA, Sacks G, Hall KD, et al. The global obesity pandemic: Shaped by global drivers and local environments. Lancet 2011;378(9793):804-814. https://doi.org/10.1016/S0140-6736(11)60813-1 6. Church TS, Thomas DM, Tudor-Locke C, et al. Trends over 5 decades in US occupation-related
physical activity and their associations with obesity. PLoS ONE 2011;6(5):e19657. https://doi.
org/10.1371/journal.pone.0019657
7. Andermann ML, Lowell BB. Toward a wiring diagram understanding of appetite control. Neuron 2017;95(4):757-778. https://doi.org/10.1016/j.neuron.2017.06.014
8. Berthoud HR, Munzberg H, Morrison CD. Blaming the brain for obesity: Integration of hedonic and homeostatic mechanisms. Gastroenterology 2017;152(7):1728-1738. https://doi.org/10.1053/j. gastro.2016.12.050
9. Sternson SM, Eiselt AK. Three pillars for the neural control of appetite. Annu Rev Physiol 2017;79:401- 423. https://doi.org/10.1146/annurev-physiol-021115-104948
10. Dhillo W, Small C, Stanley S, et al. Hypothalamic interactions between neuropeptide Y, agouti‐ related protein, cocaine‐ and amphetamine‐regulated transcript and alpha‐melanocyte‐stimulating hormone in vitro in male rats. J Neuroendocrinol 2002;14(9):725-730. https://doi.org/10.1046/j.1365- 2826.2002.00832.x
11. Papies E, Stroebe W, Aarts H. Pleasure in the mind: Restrained eating and spontaneous hedonic thoughts about food. J Exp Soc Psychol 2007;43(5):810-817. https://doi.org/10.1016/j.jesp.2006.08.001 12. Barbano MF, Cador M. Opioids for hedonic experience and dopamine to get ready for it.
Psychopharmacology (Berl) 2007;191(3):497-506. https://doi.org/10.1007/s00213-006-0521-1
13. Meye FJ, Adan RAH. Feelings about food: The ventral tegmental area in food reward and emotional
eating. Trends Pharmacol Sci 2014;35(1):31-40. https://doi.org/10.1016/j.tips.2013.11.003
14. Gosnell B, Levine A. Reward systems and food intake: Role of opioids. Int J Obes (Lond) 2009;33(Suppl
2):S54-S58. https://doi.org/10.1038/ijo.2009.73
15. Bello NT, Hajnal A. Dopamine and binge eating behaviors. Pharmacol Biochem Behav 2010;97(1):25-
33. https://doi.org/10.1016/j.pbb.2010.04.016
16. Volkow ND, Wang GJ, Baler RD. Reward, dopamine and the control of food intake: Implications for
obesity. Trends Cogn Sci 2011;15(1):37-46. https://doi.org/10.1016/j.tics.2010.11.001
17. Hurley SW, Johnson AK. The role of the lateral hypothalamus and orexin in ingestive behavior: A model for the translation of past experience and sensed deficits into motivated behaviors. Front Syst
Neurosci 2014;8:216. https://doi.org/10.3389/fnsys.2014.00216
18. Cserjési R, Luminet O, Poncelet A-S, Lénárd L. Altered executive function in obesity: Exploration of
the role of affective states on cognitive abilities. Appetite 2009;52(2):535-539. https://doi.org/10.1016/j.
appet.2009.01.003
19. Fagundo AB, de la Torre R, Jimenez-Murcia S, et al. Executive functions profile in extreme eating/ weight conditions: From anorexia nervosa to obesity. PLoS ONE 2012;7(8):e43382. https://doi. org/10.1371/journal.pone.0043382
20. Mebel DM, Wong JCY, Dong YJ, Borgland SL. Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake. Eur J Neurosci 2012;36(3):2336-2346. https://doi.org/10.1111/j.1460-9568.2012.08168.x
21. Cedernaes J, Huang W, Ramsey KM, et al. Transcriptional basis for rhythmic control of hunger and metabolism within the AgRP neuron. Cell Metab 2019;29(5):1078-1091.e5. https://doi.org/10.1016/j. cmet.2019.01.023
22. Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci 2015;36(7):461-470.
https://doi.org/10.1016/j.tips.2015.04.014
23. Secher A, Jelsing J, Baquero AF, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide- dependent weight loss. J Clin Invest 2014;124(10):4473-4488. https://doi.org/10.1172/JCI75276
24. Bliss ES, Whiteside E. The gut-brain axis, the human gut microbiota and their integration in the development of obesity. Front Physiol 2018;9:900. https://doi.org/10.3389/fphys.2018.00900
25. Fall T, Mendelson M, Speliotes EK. Recent advances in human genetics and epigenetics of adiposity: Pathway to precision medicine? Gastroenterology 2017;152(7):1695-1706. https://doi.org/10.1053/j. gastro.2017.01.054
26. Thornton LM, Mazzeo SE, Bulik CM. The heritability of eating disorders: Methods and current findings. Curr Top Behav Neurosci 2010;6:141-156. https://doi.org/10.1007/7854_2010_91
27. Thaker VV. Genetic and epigenetic causes of obesity. Adolesc Med State Art Rev 2017;28(2):379-405. 28. Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest
2002;110(8):1093-1103. https://doi.org/10.1172/JCI15693
29. Van der Klaauw AA, Farooqi IS. The hunger genes: Pathways to obesity. Cell 2015;161(1):119-132.
https://doi.org/10.1016/j.cell.2015.03.008
30.Karam JG. Secondary causes of obesity. Clin Pract 2007;4(5):641. https://doi.
org/10.2217/14750708.4.5.641
31. Clarys JP, Martin AD, Marfell-Jones MJ, Janssens V, Caboor D, Drinkwater DT. Human body composition: A review of adult dissection data. Am J Hum Biol 1999;11(2):167-174. https://doi. org/10.1002/(SICI)1520-6300(1999)11:2<167::AID-AJHB4>3.0.CO;2-G
32. Ma X, Lee P, Chisholm DJ, James DE. Control of adipocyte differentiation in different fat depots: Implications for pathophysiology or therapy. Front Endocrinol (Lausanne) 2015;6:1. https://doi. org/0.3389/fendo.2015.00001
33. Seufert J. Leptin effects on pancreatic beta-cell gene expression and function. Diabetes 2004;53(Suppl 1):S152-S158. https://doi.org/10.2337/diabetes.53.2007.s152
34. Crewe C, An YA, Scherer PE. The ominous triad of adipose tissue dysfunction: Inflammation, fibrosis, and impaired angiogenesis. J Clin Invest 2017;127(1):74-82. https://doi.org/doi:10.1172/JCI88883
35. Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis. BMC Public Health 2009;9:88. https://doi.org/10.1186/1471-2458-9-88
36. Ikeda K, Maretich P, Kajimura S. The common and distinct features of brown and beige adipocytes. Trends Endocrinol Metab 2018;29(3):191-200. https://doi.org/10.1016/j.tem.2018.01.001
37. Cresci GA, Bawden E. Gut microbiome: What we do and don’t know. Nutr Clin Pract 2015;30(6):734- 746. https://doi.org/10.1177/0884533615609899
38. BouterKE,vanRaalteDH,GroenAK,NieuwdorpM.Roleofthegutmicrobiomeinthepathogenesisof obesity and obesity-related metabolic dysfunction. Gastroenterology 2017;152(7):1671-1678. https://doi. org/10.1053/j.gastro.2016.12.048
39. Fasano A. The physiology of hunger. N Engl J Med 2025;392(4):372-381. https://doi.org/10.1056/ NEJMra2402679
40. BäckhedF,DingH,WangT,etal.Thegutmicrobiotaasanenvironmentalfactorthatregulatesfatstorage. Proc Natl Acad Sci U S A 2004;101(44):15718-15723. https://doi.org/10.1073/pnas.0407076101
41. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardia ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006;444(7122):1027-1031. https://doi. org/10.1038/nature05414
42. XuZ,JiangW,HuangW,LinY,ChanFKL,NgSC.Gutmicrobiotainpatientswithobesityandmetabolic disorders – a systematic review. Genes Nutr 2022;17(1):2. https://doi.org/10.1186/s12263-021-00703-6
43. DalbyMJ.Questioningthefoundationsofthegutmicrobiotaandobesity.PhilosTransRSocLondBBiol Sci 2023;378(1888):20220221. https://doi.org/10.1098/rstb.2022.0221
44. Zhang Z, Mocanu V, Cai C, et al. Impact of fecal microbiota transplantation on obesity and metabolic syndrome – a systematic review. Nutrients 2019;11(10):2291. https://doi.org/10.3390/nu11102291
45. JohnGK,WangL,NanavatiJ,TwoseC,SinghR,MullinG.Dietaryalterationofthegutmicrobiomeand its impact on weight and fat mass: A systematic review and meta-analysis. Genes (Basel) 2018;9(3):167. https://doi.org/10.3390/genes9030167
46. Al-Assal K, Martinez AC, Torrinhas RS, Cadrdinelli C, Waitzberg D. Gut microbiota and obesity. Clin Nutr Exp 2018;20:60-64. https://doi.org/10.1016/j.yclnex.2018.03.001
47. Guo Y, Huang ZP, Liu CQ, Qi L, Sheng Y, Zou DJ. Modulation of the gut microbiome: A systematic review of the effect of bariatric surgery. Eur J Endocrinol 2018;178(1):43-56. https://doi.org/10.1530/ EJE-17-0403
48. Angelakis E, Armougom F, Million M, Raoult D. The relationship between gut microbiota and weight gain in humans. Future Microbiol 2012;7(1):91-109. https://doi.org/10.2217/fmb.11.142
49. Longo M, Zatterale F, Naderi J, et al. Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int J Mol Sci 2019;20(9):2358. https://doi.org/10.3390/ijms20092358
50. Chen L, Chen R, Wang H, Liang F. Mechanisms linking inflammation to insulin resistance. Int J Endocrinol 2015;2015:508409. https://doi.org/10.1155/2015/508409
51. ElluluMS,PatimahI,Khaza’aiH,RahmatA,AbedY.Obesityandinflammation:Thelinkingmechanism and the complications. Arch Med Sci 2017;13(4):851-863. https://doi.org/10.5114/aoms.2016.58928
52. Zhang Z, Scherer PE. The dysfunctional adipocyte – a cancer cell’s best friend. Nat Rev Endocrinol
2018;14(3):132-134. https://doi.org/10.1038/nrendo.2017.174
53. Knowler WC, Barrett-Connor E, Fowler SE, et al.; Diabetes Prevention Program Research Group.
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med
2002;346(6):393-403. https://doi.org/10.1056/NEJMoa012512
54. KnowlerW,FowlerS,HammanR,etal.;DiabetesPreventionProgramResearchGroup.10-yearfollow-
up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet
2009;374(9702):1677-1686. https://doi.org/10.1016/s0140-6736(09)61457-4
55. GilliesCL,AbramsKR,LambertPC,etal.Pharmacologicalandlifestyleinterventionstopreventordelay
type 2 diabetes in people with impaired glucose tolerance: Systematic review and meta-analysis. BMJ
2007;334(7588):299. https://doi.org/10.1136/bmj.39063.689375.55
56. Taylor R, Holman RR. Normal weight individuals who develop type 2 diabetes: The personal fat
threshold. Clin Sci (Lond) 2015;128(7):405-410. https://doi.org/10.1042/CS20140553
57. Taylor R. Type 2 diabetes and remission: Practical management guided by pathophysiology. J Intern Med
2021;289(6):754-770. https://doi.org/10.1111/joim.13214
58. Lim EL, Hollingsworth K, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes:
Normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol.
Diabetologia 2011;54(10):2506-2514. https://doi.org/10.1007/s00125-011-2204-7
59. Steven S, Hollingsworth KG, Al-Mrabeh A, et al. Very low-calorie diet and 6 months of weight stability in type 2 diabetes: Pathophysiological changes in responders and nonresponders. Diabetes Care
2016;39(5):808-815. https://doi.org/10.2337/dc15-1942
60. Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2
diabetes (DiRECT): An open-label, cluster-randomised trial. Lancet 2018;391(10120):541-551. https://
doi.org/10.1016/S0140-6736(17)33102-1
61. Lean ME, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol 2019;7(5):344-355. https://doi.org/10.1016/S2213-8587(19)30068-3
62. Taylor R, Barnes AC, Hollingsworth KG, et al. Aetiology of type 2 diabetes in people with a ‘normal’ body mass index: Testing the personal fat threshold hypothesis. Clin Sci (Lond) 2023;137(16):1333- 1346. https://doi.org/10.1042/CS20230586
63. Speakman JR, Hall KD. Models of body weight and fatness regulation. Philos Trans R Soc Lond B Biol Sci 2023;378(1888):20220231. https://doi.org/10.1098/rstb.2022.0231
64. Lund J, Lund C, Morville T, Clemmensen C. The unidentified hormonal defense against weight gain. PLoS Biol 2020;18(2):e3000629. https://doi.org/10.1371/journal.pbio.3000629
65. Blundell JE, Gibbons C, Beaulieu K, et al. The drive to eat in homo sapiens: Energy expenditure drives energy intake. Physiol Behav 2020;219:112846. https://doi.org/10.1016/j.physbeh.2020.112846
66. Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci 1953;140(901):578-596. https://doi.org/10.1098/rspb.1953.0009
67. Chow CC, Hall KD. Short and long-term energy intake patterns and their implications for human body weight regulation. Physiol Behav 2014;134:60-65. https://doi.org/10.1016/j.physbeh.2014.02.044
68. Díaz-ZavalaRG,Castro-CantúMF,ValenciaME,Álvarez-HernándezG,HabyMM,Esparza-Romero J. Effect of the holiday season on weight gain: A narrative review. J Obes 2017;2017:2085136. https://
doi.org/10.1155/2017/2085136
69. Rees SG, Holman RR, Turner RC. The Christmas feast. Br Med J (Clin Res Ed) 1985;291(6511):1764- 1765. https://doi.org/10.1136/bmj.291.6511.1764
70. Yanovski JA, Yanovski SZ, Sovik KN, Nguyen TT, O’Neil PM, Sebring NG. A prospective study of holiday weight gain. N Engl J Med 2000;342(12):861-867. https://doi.org/10.1056/ NEJM200003233421206
71. Wagner DR, Larson JN, Wengreen H. Weight and body composition change over a six-week holiday period. Eating Weight Disord 2012;17(1):e54-e56. https://doi.org/10.1007/BF03325328
72. Coleman DL. A historical perspective on leptin. Nat Med 2010;16(10):1097-1099. https://doi. org/10.1038/nm1010-1097
73. Myers MG, Heymsfield SB, Haft C, et al. Challenges and opportunities of defining clinical leptin resistance. Cell Metab 2012;15(2):150-156. https://doi.org/10.1016/j.cmet.2012.01.002
74. Speakman JR, Elmquist JK. Obesity: An evolutionary context. Life Metab 2022;1(1):10-24. https:// doi.org/10.1093/lifemeta/loac002
75. GBD 2015 Obesity Collaborators; Afshin A, Fourouzanfar MH, Reitsma MB, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017;377(1):13-27. https://doi. org/10.1056/NEJMoa1614362
76. Sellayah D, Cagampang FR, Cox RD. On the evolutionary origins of obesity: A new hypothesis. Endocrinology 2014;155(5):1573-1588. https://doi.org/10.1210/en.2013-2103
77. SpeakmanJR.Evolutionaryperspectivesontheobesityepidemic:Adaptive,maladaptive,andneutral viewpoints. Annu Rev Nutr 2013;33:289-317. https://doi.org/10.1146/annurev-nutr-071811-150711 78. NeelJV.Diabetesmellitus:A‘thrifty’genotyperendereddetrimentalby‘progress’?AmJHumGenet
1962;14(4):353-362.
79. Mahmoud AM. An overview of epigenetics in obesity: The role of lifestyle and therapeutic
interventions. Int J Mol Sci 2022;23(3):1341. https://doi.org/10.3390/ijms23031341
80. Wu F-Y, Yin R-X. Recent progress in epigenetics of obesity. Diabetol Metab Syndr 2022;14(1):171.
https://doi.org/10.1186/s13098-022-00947-1
81. Langley‐Evans SC. Early life programming of health and disease: The long‐term consequences of obesity in pregnancy. J Hum Nutr Diet 2022;35(5):816-832. https://doi.org/10.1111/jhn.13023
82. Ounjaijean S, Wongthanee A, Kulprachakarn K, et al. Higher maternal BMI early in pregnancy is
associated with overweight and obesity in young adult offspring in Thailand. BMC Public Health
2021;21(1):724. https://doi.org/10.1186/s12889-021-10678-z
83. Derraik JG, Ahlsson F, Diderholm B, Lundgren M. Obesity rates in two generations of Swedish
women entering pregnancy and associated obesity risk among adult daughters. Sci Rep 2015;5:16692.
https://doi.org/10.1038/srep16692
84. Hall KD, Farooqi IS, Friedman JM, et al. The energy balance model of obesity: Beyond calories in, calories out. Am J Clin Nutr 2022;115(5):1243-1254. https://doi.org/10.1093/ajcn/nqac031
85. Ludwig DS, Apovian CM, Aronne LJ, et al. Competing paradigms of obesity pathogenesis: Energy balance versus carbohydrate-insulin models. Eur J Clin Nutr 2022;76(9):1209-1221. https://doi. org/10.1038/s41430-022-01179-2
86. Magkos F, Sørensen TI, Raubenheimer D, et al. On the pathogenesis of obesity: Causal models and missing pieces of the puzzle. Nat Metab 2024;6(10):1856-1865. https://doi.org/10.1038/s42255-024- 01106-8
87. Friedman MI, Sørensen TI, Taubes G, Lund J, Ludwig DS. Trapped fat: Obesity pathogenesis as an intrinsic disorder in metabolic fuel partitioning. Obes Rev 2024;25(10):e13795. https://doi. org/10.1111/obr.13795
88. Heindel JJ, Lustig RH, Howard S, Corkey BE. Obesogens: A unifying theory for the global rise in obesity. Int J Obes (Lond) 2024;48(4):449-460. https://doi.org/10.1038/s41366-024-01460-3
89. Dhurandhar NV, Petersen KS, Webster C. Key causes and contributors of obesity: A perspective. Nurs Clin North Am 2021;56(4):449-464. https://doi.org/10.1016/j.cnur.2021.07.007
90. Akalestou E, Miras AD, Rutter GA, le Roux CW. Mechanisms of weight loss after obesity surgery. Endocr Rev 2022;43(1):19-34. https://doi.org/10.1210/endrev/bnab022
91. Aldawsari M, Almadani FA, Almuhammadi N, Algabsani S, Alamro Y, Aldhwayan M. The efficacy of GLP-1 analogues on appetite parameters, gastric emptying, food preference and taste among adults with obesity: Systematic review of randomised controlled trials. Diabetes Metab Syndr Obes 2023;16:575-595. https://doi.org/10.2147/DMSO.S387116
92. Ryan DH, Lingvay I, Deanfield J, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med 2024;30(7):2049-2057. https://doi.org/10.1038/ s41591-024-02996-7
93. Sjöström L. Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery. J Intern Med 2013;273(3):219-234. https://doi. org/10.1111/joim.12012
94. Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: A meta- analysis of US studies. Am J Clin Nutr 2001;74(5):579-584. https://doi.org/10.1093/ajcn/74.5.579 95. Mann T, Tomiyama AJ, Westling E, Lew A-M, Samuells B, Chatman J. Medicare’s search for
effective obesity treatments: Diets are not the answer. Am Psychol 2007;62(3):220-233. https://doi.
org/10.1037/0003-066X.62.3.220
96. Aronne LJ, Hall KD, Jakicic J, et al. Describing the weight‐reduced state: Physiology, behavior, and interventions. Obesity (Silver Spring) 2021;29(Suppl 1):S9-S24. https://doi.org/10.1002/oby.23086
97. Massey RJ, Siddiqui MK, Pearson ER, Dawed AY. Weight variability and cardiovascular outcomes: A systematic review and meta-analysis. Cardiovasc Diabetol 2023;22(1):5. https://doi.org/10.1186/ s12933-022-01735-x
98. Shumnalieva R, Kotov G, Ermencheva P, Monov S. Pathogenic mechanisms and therapeutic approaches in obesity-related knee osteoarthritis. Biomedicines 2023;12(1):9. https://doi. org/10.3390/biomedicines12010009
99. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023;389(24):2221-2232. https://doi.org/10.1056/ NEJMoa2307563
100. LeBlanc ES, Patnode CD, Webber EM, Redmond N, Rushkin M, O’Connor EA. Behavioral and pharmacotherapy weight loss interventions to prevent obesity-related morbidity and mortality in adults: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2018;320(11):1172-1191. https://doi.org/10.1001/jama.2018.7777
101. Apovian CM, Aronne L, Rubino D, et al. A randomised, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity‐related risk factors (COR‐II). Obesity (Silver Spring) 2013;21(5):935-943. https://doi.org/10.1002/oby.20309
102. Javor E, Lucijanić M, Skelin M. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;385(1):e4. https://doi.org/10.1056/NEJMc2106918
103. Wadden TA, Bailey TS, Billings LK, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: The STEP 3 randomised clinical trial. JAMA 2021;325(14):1403-1413. https://doi.org/10.1001/jama.2021.1831
104. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: The COR‐BMOD trial. Obesity (Silver Spring) 2011;19(1):110-120. https://doi.org/10.1038/oby.2010.147
Downloads
Published
Issue
Section
License
Copyright (c) 2025 W May, J H Goedecke, M Conradie-Smit

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Licensing Information
The SAMJ is published under an Attribution-Non Commercial International Creative Commons Attribution (CC-BY-NC 4.0) License. Under this license, authors agree to make articles available to users, without permission or fees, for any lawful, non-commercial purpose. Users may read, copy, or re-use published content as long as the author and original place of publication are properly cited.
Exceptions to this license model is allowed for UKRI and research funded by organisations requiring that research be published open-access without embargo, under a CC-BY licence. As per the journals archiving policy, authors are permitted to self-archive the author-accepted manuscript (AAM) in a repository.
Publishing Rights
Authors grant the Publisher the exclusive right to publish, display, reproduce and/or distribute the Work in print and electronic format and in any medium known or hereafter developed, including for commercial use. The Author also agrees that the Publisher may retain in print or electronic format more than one copy of the Work for the purpose of preservation, security and back-up.




