Effects of GLP-1 analogs combined with physical exercise on total body mass in individuals with obesity: a systematic review
DOI:
https://doi.org/10.1590/1980-0037.2025v27e103939Keywords:
Glucagon Like Peptide 1, Obesity, Physical Activity, Weight LossAbstract
Comprehensive evidence integrating results to assess the combined effects of physical exercise and pharmacological therapy on body mass reduction is scarce. Therefore, this review aims to analyze the effects of glucagon-like peptide-1 (GLP-1) analogues, specifically liraglutide and semaglutide, in conjunction with physical exercise on changes in body mass among patients with obesity. This systematic literature review is registered in PROSPERO (International prospective register of systematic reviews) under ID: CRD42023454783. Searches were conducted between September and October 2023, without restriction on publication year and language, across the following databases: Medline via PubMed, Semantic Scholar, Web of Science, Scopus, and Embase. Nine articles involving 4,236 participants with obesity (with or without diabetes) were included. Participants, aged 18 to 65 years with BMI over 27 kg/m², were treated with liraglutide or semaglutide. Liraglutide was increased to 3.0 mg, and semaglutide to 2.4 mg. The combination of liraglutide and exercise led to an average weight loss of 5 kg over 53 weeks. Higher doses of liraglutide and semaglutide effectively reduce total body mass in individuals with obesity. Combining GLP-1 analogs with physical exercise enhances these weight loss outcomes.
References
Kolotkin RL, Meter K, Williams GR. Quality of life and obesity. Obes Rev. 2001;2(4):219-29.
Purnell JQ. Definitions, Classification, and Epidemiology of Obesity. [Updated 2023 May 4]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279167/
Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D, Toplak H; Obesity Management Task Force of the European Association for the Study of Obesity. European Guidelines for Obesity Management in Adults. Obes Facts. 2015;8(6):402-24.
Sánchez-Garrido MA, Brandt SJ, Clemmensen C, Müller TD, DiMarchi RD, Tschöp MH. GLP-1/glucagon receptor co-agonism for treatment of obesity. Diabetologia 2017; 60(10):1851–1861.
Bellicha A, van Baak MA, Battista F, Beaulieu K, Blundell JE, Busetto L, Carraça EV, Dicker D, Encantado J, Ermolao A, Farpour-Lambert N, Pramono A, Woodward E, Oppert JM. Effect of exercise training on weight loss, body composition changes, and weight maintenance in adults with overweight or obesity: An overview of 12 systematic reviews and 149 studies. Obes Rev. 2021l;22(Suppl 4):e13256.
Jakicic JM, Kraus WE, Powell KE, Campbell WW, Janz KF, Troiano RP, Sprow K, Torres A, Piercy KL; 2018 Physical Activity Guidelines Advisory Committee. Association between Bout Duration of Physical Activity and Health: Systematic Review. Med Sci Sports Exerc. 2019;51(6):1213-1219.
Oppert JM, Bellicha A, Ciangura C. Physical activity in management of persons with obesity. Eur J Intern Med. 2021;93:8-12.
Jensen SBK, Janus C, Lundgren JR, Juhl CR, Sandsdal RM, Olsen LM, Andresen A, Borg SA, Jacobsen IC, Finlayson G, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS. Exploratory analysis of eating- and physical activity-related outcomes from a randomized controlled trial for weight loss maintenance with exercise and liraglutide single or combination treatment. Nat Commun. 2022;13(1):4770.
Williams DM, Nawaz A, Evans M. Drug Therapy in Obesity: A Review of Current and Emerging Treatments. Diabetes Ther. 2020;11(6):1199-1216.
Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D, Toplak H; Obesity Management Task Force of the European Association for the Study of Obesity. European Guidelines for Obesity Management in Adults. Obes Facts. 2015;8(6):402-24.
Hainer V, Toplak H, Mitrakou A. Treatment modalities of obesity: what fits whom? Diabetes Care. 2008;31 Suppl 2: S269-77.
Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409-39.
Reed J, Bain S, Kanamarlapudi V. Recent advances in understanding the role of glucagon-like peptide 1. F1000Res. 2020;9:F1000 Faculty Rev-239.
Graaf Cd, Donnelly D, Wootten D, Lau J, Sexton PM, Miller LJ, Ahn JM, Liao J, Fletcher MM, Yang D, Brown AJ, Zhou C, Deng J, Wang MW. Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes. Pharmacol Rev. 2016;68(4):954-1013.
Gupta V. Glucagon-like peptide-1 analogues: An overview. Indian J Endocrinol Metab. 2013;17(3):413-21.
Drucker DJ. GLP-1 physiology informs the pharmacotherapy of obesity. Mol Metab. 2022; 57:101351.
Galvão TF, Tiguman GMB, Sarkis-Onofre R. A declaração PRISMA 2020: diretriz atualizada para relatar revisões sistemáticas. Epidemiol Serv Saúde 2022;31(2):e2022107.
Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther. 2003;83(8):713-21.
Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.
Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020;54(24):1451-1462.
Sandsdal RM, Juhl CR, Jensen SBK, Lundgren JR, Janus C, Blond MB, et al., Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial. Cardiovasc Diabetol. 2023;22(1):41.
Lundgren JR, Janus C, Jensen SBK, Juhl CR, Olsen LM, Christensen RM, et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med. 2021;384(18):1719-1730.
Jensen SBK, Juhl CR, Janus C, Lundgren JR, Martinussen C, Wiingaard C, et al. Weight loss maintenance with exercise and liraglutide improves glucose tolerance, glucagon response, and beta cell function. Obesity (Silver Spring). 2023;31(4):977-989.
Khoo J, Hsiang JC, Taneja R, Koo SH, Soon GH, Kam CJ, et al. Randomized trial comparing effects of weight loss by liraglutide with lifestyle modification in non-alcoholic fatty liver disease. Liver Int. 2019;39(5):941-949.
Davies MJ, Bergenstal R, Bode B, Kushner RF, Lewin A, Skjøth TV, et al. Efficacy of Liraglutide for Weight Loss Among Patients with Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA. 2015;314(7):687-99.
Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, et al. Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012;36(6):843-54.
Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.
Mensberg P, Nyby S, Jørgensen PG, Storgaard H, Jensen MT, Sivertsen J, et al. Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes. Diabetes Obes Metab. 2017;19(2):172-180.
Tronieri JS, Fabricatore AN, Wadden TA, Auerbach P, Endahl L, Sugimoto D, et al. Effects of Dietary Self-Monitoring, Physical Activity, Liraglutide 3.0 mg, and Placebo on Weight Loss in the SCALE IBT Trial. Obes Facts. 2020;13(6):572-583.
Vidal P, Stanford KI. Exercise-Induced Adaptations to Adipose Tissue Thermogenesis. Front Endocrinol (Lausanne). 2020;11:270.
Wen X, Zhang B, Wu B, Xiao H, Li Z, Li R, Xu X, Li T. Signaling pathways in obesity: mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2022;7(1):298.
