Is physical activity still the key to treating obesity? - semaglutide, a new position among therapies
DOI:
https://doi.org/10.12775/QS.2024.20.54194Keywords
semaglutide, GLP-1, sport, obesity, diabetes mellitus, activitiesAbstract
Obesity is a condition characterized by excessive and abnormal accumulation of fat tissue. It disrupts energy homeostasis, leading to severe health problems. Physical activity is a significant part of reducing obesity. If sport activities are not enough, pharmacological management may be needed. One of pharmacological approaches to obesity treatment is a use of semaglutide. It is a glucagon-like peptide 1 receptor agonists (GLP-1RAs) approved for the treatment of type 2 diabetes. Semaglutide presents many pleiotropic effects and has an impact on several organ systems, such as cardiovascular, digestive, or nervous systems. Clinicals should remember about semaglutide’s complex mechanisms of actions and different adverse effects.
References
Weir CB, Jan A. BMI Classification Percentile And Cut Off Points.; 2024.
Jastreboff AM, Kotz CM, Kahan S, Kelly AS, Heymsfield SB. Obesity as a Disease: The Obesity Society 2018 Position Statement. Obesity. 2019;27(1):7-9. doi:10.1002/oby.22378
De Lorenzo A, Gratteri S, Gualtieri P, Cammarano A, Bertucci P, Di Renzo L. Why primary obesity is a disease? J Transl Med. 2019;17(1):169. doi:10.1186/s12967-019-1919-y
Obesity and overweight. Accessed July 28, 2024. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
Finkelstein EA, Khavjou OA, Thompson H, et al. Obesity and Severe Obesity Forecasts Through 2030. Am J Prev Med. 2012;42(6):563-570. doi:10.1016/j.amepre.2011.10.026
Ramasamy A, Laliberté F, Aktavoukian SA, et al. Direct and Indirect Cost of Obesity Among the Privately Insured in the United States. J Occup Environ Med. 2019;61(11):877-886. doi:10.1097/JOM.0000000000001693
Nagi MA, Ahmed H, Rezq MAA, et al. Economic costs of obesity: a systematic review. Int J Obes. 2024;48(1):33-43. doi:10.1038/s41366-023-01398-y
Okunogbe A, Nugent R, Spencer G, Powis J, Ralston J, Wilding J. Economic impacts of overweight and obesity: current and future estimates for 161 countries. BMJ Glob Health. 2022;7(9):e009773. doi:10.1136/bmjgh-2022-009773
Kłosińska M, Domańska I, Gałuszka A, et al. Analysis of the role of education and sport in the heavy burden of obesity. Journal of Education, Health and Sport. 2023;43(1):194-207. doi:10.12775/JEHS.2023.43.01.015
Blundell J, Finlayson G, Axelsen M, et al. Effects of once‐weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017;19(9):1242-1251. doi:10.1111/dom.12932
Gabery S, Salinas CG, Paulsen SJ, et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020;5(6). doi:10.1172/jci.insight.133429
Rowlands J, Heng J, Newsholme P, Carlessi R. Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function. Front Endocrinol (Lausanne). 2018;9. doi:10.3389/fendo.2018.00672
Andraos J, Muhar H, Smith SR. Beyond glycemia: Comparing tirzepatide to GLP-1 analogues. Rev Endocr Metab Disord. 2023;24(6):1089-1101. doi:10.1007/s11154-023-09825-1
Tamayo-Trujillo R, Ruiz-Pozo VA, Cadena-Ullauri S, et al. Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity. Front Nutr. 2024;11. doi:10.3389/fnut.2024.1398059
Alharbi SH. Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications. Ther Adv Endocrinol Metab. 2024;15. doi:10.1177/20420188231222367
Kommu S, Whitfield P. Semaglutide.; 2024.
Tamayo-Trujillo R, Ruiz-Pozo VA, Cadena-Ullauri S, et al. Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity. Front Nutr. 2024;11. doi:10.3389/fnut.2024.1398059
Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. Diabetes Care. 2019;42(9):1724-1732. doi:10.2337/dc19-0749
Yabe D, Nakamura J, Kaneto H, et al. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020;8(5):392-406. doi:10.1016/S2213-8587(20)30074-7
Zinman B, Aroda VR, Buse JB, et al. Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Diabetes Care. 2019;42(12):2262-2271. doi:10.2337/dc19-0898
Mosenzon O, Blicher TM, Rosenlund S, et al. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019;7(7):515-527. doi:10.1016/S2213-8587(19)30192-5
Rossing P, Caramori ML, Chan JCN, et al. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5):S1-S127. doi:10.1016/j.kint.2022.06.008
Rossing P, Baeres FMM, Bakris G, et al. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrology Dialysis Transplantation. 2023;38(9):2041-2051. doi:10.1093/ndt/gfad009
Mosenzon O, Capehorn MS, De Remigis A, Rasmussen S, Weimers P, Rosenstock J. Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials. Cardiovasc Diabetol. 2022;21(1):172. doi:10.1186/s12933-022-01585-7
Wu W, Tong H mu, Li Y sheng, Cui J. The effect of semaglutide on blood pressure in patients with type-2 diabetes: a systematic review and meta-analysis. Endocrine. 2023;83(3):571-584. doi:10.1007/s12020-023-03636-9
Ryan DH, Lingvay I, Colhoun HM, et al. Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design. Am Heart J. 2020;229:61-69. doi:10.1016/j.ahj.2020.07.008
Aroda VR, Ahmann A, Cariou B, et al. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1–7 trials. Diabetes Metab. 2019;45(5):409-418. doi:10.1016/j.diabet.2018.12.001
Lingvay I, Brown‐Frandsen K, Colhoun HM, et al. Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics. Obesity. 2023;31(1):111-122. doi:10.1002/oby.23621
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. doi:10.1038/s41591-024-02996-7
Borlaug BA, Kitzman DW, Davies MJ, et al. Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nat Med. 2023;29(9):2358-2365. doi:10.1038/s41591-023-02526-x
Morten Schou MCPBABJBMJDDWKSJSSVSPKMCSHSZAKLMNK. Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program.
Lorenz M, Lawson F, Owens D, et al. Differential effects of glucagon-like peptide-1 receptor agonists on heart rate. Cardiovasc Diabetol. 2017;16(1):6. doi:10.1186/s12933-016-0490-6
Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. New England Journal of Medicine. 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395
Niu S, Chen S, Chen X, et al. Semaglutide ameliorates metabolism and hepatic outcomes in an NAFLD mouse model. Front Endocrinol (Lausanne). 2022;13. doi:10.3389/fendo.2022.1046130
Diehl T, Mullins R, Kapogiannis D. Insulin resistance in Alzheimer’s disease. Translational Research. 2017;183:26-40. doi:10.1016/j.trsl.2016.12.005
Hölscher C. Novel dual GLP-1/GIP receptor agonists show neuroprotective effects in Alzheimer’s and Parkinson’s disease models. Neuropharmacology. 2018;136:251-259. doi:10.1016/j.neuropharm.2018.01.040
Zhang L, Zhang L, Li L, Hölscher C. Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson’s disease mouse model. Neuropeptides. 2018;71:70-80. doi:10.1016/j.npep.2018.07.003
Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol (Lausanne). 2021;12. doi:10.3389/fendo.2021.645563
Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine. 2016;375(19):1834-1844. doi:10.1056/NEJMoa1607141
Aroda VR, Bain SC, Cariou B, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(5):355-366. doi:10.1016/S2213-8587(17)30085-2
Husain M, Birkenfeld AL, Donsmark M, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine. 2019;381(9):841-851. doi:10.1056/NEJMoa1901118
Zhao Z, Tang Y, Hu Y, Zhu H, Chen X, Zhao B. Hypoglycemia following the use of glucagon-like peptide-1 receptor agonists: a real-world analysis of post-marketing surveillance data. Ann Transl Med. 2021;9(18):1482-1482. doi:10.21037/atm-21-4162
Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol (Lausanne). 2021;12. doi:10.3389/fendo.2021.645563
Shu Y, He X, Wu P, Liu Y, Ding Y, Zhang Q. Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system. Front Public Health. 2022;10. doi:10.3389/fpubh.2022.996179
Patel F, Gan A, Chang K, Vega KJ. Acute Pancreatitis in a Patient Taking Semaglutide. Cureus. Published online August 19, 2023. doi:10.7759/cureus.43773
Yang Z, Lv Y, Yu M, et al. GLP-1 receptor agonist-associated tumor adverse events: A real-world study from 2004 to 2021 based on FAERS. Front Pharmacol. 2022;13. doi:10.3389/fphar.2022.925377
Mazokopakis EE. Semaglutide-induced Subclinical Hypothyroidism: A Case Report. European Journal of Medical and Health Sciences. 2023;5(3):8-9. doi:10.24018/ejmed.2023.5.3.1743
Billewicz M, Turek A, Makowska K, et al. Skin appendage abnormalities in hypothyroidism: understanding and management. Journal of Education, Health and Sport. 2024;73:51714. doi:10.12775/JEHS.2024.73.51714
Li JR, Cao J, Wei J, Geng W. Case Report: Semaglutide-associated depression: a report of two cases. Front Psychiatry. 2023;14. doi:10.3389/fpsyt.2023.1238353
Sorli C, Harashima S ichi, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(4):251-260. doi:10.1016/S2213-8587(17)30013-X
Meier JJ. Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation. Front Endocrinol (Lausanne). 2021;12. doi:10.3389/fendo.2021.645617
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