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Published: 31-01-2023

Use of GLP-1 analogs in the treatment of obesity: an integrative and systematic review

UNIFEV - University Center of Votuporanga-SP- Medical Course, Brazil
UNIFEV - University Center of Votuporanga-SP- Medical Course, Brazil.
UNIFEV - University Center of Votuporanga-SP- Medical Course, Brazil
UNIFEV - University Center of Votuporanga-SP- Medical Course, Brazil
UNIFEV - University Center of Votuporanga-SP- Medical Course, Brazil
UNIFIPA - Centro Universitário Padre Albino/ Padre Albino University Center, Medicine Course, Catanduva, Sao Paulo, Brazil
UNIFEV - University Center of Votuporanga-SP- Medical Course, Brazil / UNIFIPA - Centro Universitário Padre Albino/ Padre Albino University Center, Medicine Course, Catanduva, Sao Paulo, Brazil
GLP-1 analogs Obesity Treatment


Obesity is the global epidemic of the 21st century: about 1.5 billion adults worldwide are overweight, and among them, about 200 million men and 300 million women are obese. The prevalence of overweight and obesity is also increasing in children and adolescents in developed (about 25%) and developing countries (about 13%). Obesity has been associated with many comorbidities, including type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), hypertension, chronic kidney disease, cardiovascular disease (CVD), and malignancies, leading to increased mortality observed in obese individuals. Overweight and obesity were estimated to be associated worldwide with 3.4 million deaths, which could also be expressed as 4% of disability-adjusted life-years lost (DALYs). It is also alarming that children with severe obesity are apparently at in- creased risk of premature death. Managing obesity is hard and usually disappointing for both patients and physicians. Weight loss is difficult to achieve and even more difficult to sustain in the long term. When lifestyle modifications fail to achieve the predefined target, anti-obesity medications may be added on, as recommended by all relevant guidelines, including those of the Endocrine Society and recent guidelines for obese with diabetes. Glucagon-like peptide 1 (GLP-1) is an incretin secreted by L-cells in the intestinal mucosa and has been shown to act in the brain and periphery to cause effective weight loss. GLP-1 release is stimulated by food intake and its agonist, exenatide, is the first from the incretin family approved for weight-loss therapy by the Food and Drug Administration (FDA). In overweight and obese adults, it is concluded that the GLP-1 analogs and the Phentermine/Topiramate association proved to be among the best for the effects on weight reduction. Regarding childhood obesity, the FDA recently approved the use of Liraglutide. Schizophrenic patients, a target of studies due to risk factors, benefited from treatment with GLP-1 analogs.


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  1. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 2011;377:557–67.
  2. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the global burden of disease study 2013. Lancet 2014;384:766–81.
  3. Global BMIMC, Di Angelantonio E, Bhupathiraju Sh N,Wormser D, Gao P, Kaptoge S, et al. Body-mass index and all-cause mortality: individual-participantdata meta-analysis of 239 prospective studies in four continents. Lancet 2016;388:776–86.
  4. LimSS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2224–60.
  5. Bass R, Eneli I. Severe childhood obesity: an under-recognised and growing health problem. Postgrad Med J 2015;91:639–45.
  6. Ma C, Avenell A, Bolland M, Hudson J, Stewart F, Robertson C, et al. Effects of weight loss interventions for adults who are obese on mortality, disease, and cancer: systematic review and meta-analysis. BMJ 2017;359:j4849.
  7. ABESO, Diretrizes Brasileiras de obesidade, 2016.
  8. Pilitsi E, Farr OM, Polyzos SA, Perakakis N, Nolen-Doerr E, Papathanasiou AE, et al. Pharmacotherapy of obesity: available medications and drugs under investigation. Metabolism 2018:170–92.
  9. Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, et al.Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015;100:342–62.
  10. Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, et al. Management of Hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of diabetes (EASD). Diabetes Care 2018;41:2669–701.
  11. Alves da Conceição, R. et al. Fármacos para o tratamento do diabetes tipo II: uma visita ao passado e um olhar para o futuro. Revista Virtual de Química, 2017, v. 9, n.2, 514-534.
  12. Hurren KM; Pinelli NR. Efficacy and Safety of Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Compared with Exenatide Twice Daily and Sitagliptin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. The Annals of Pharmacotherapy, 2011, v.45.
  13. Siskind D, Hahn M, Correll CU, Fink-Jensen A, Russell AW, Bak N, Broberg BV, Larsen J, Ishøy PL, Vilsbøll T, Knop FK, Kisely S, Ebdrup BH. Glucagon-like peptide-1 receptor agonists for antipsychotic-associated cardio-metabolic risk factors: A systematic review and individual participant data meta-analysis. Diabetes Obes Metab. 2019 Feb;21(2):293-302. doi: 10.1111/dom.13522.
  14. Gortmaker SL, Swinburn BA, Levy D, Carter R,Mabry PL, Finegood DT, et al. Changing the future of obesity: science, policy, and action. Lancet 2011;378:838– 47.
  15. Angelucci E, Federico V, Cianfarani S, Manzoli L, Davi G, Tartaro A, et al. Shortterm administration of the GLP-1 analog liraglutide decreases circulating leptin and increases GIP levels and these changes are associated with alterations in CNS responses to food cues: A randomized, placebo-controlled, crossover study. Diabetes care. 2016;65(7):945-53.
  16. Farr OM, Sofopoulos M, Tsoukas MA, Dincer F, Thakkar B, Sahin-Efe A, et al. GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebocontrolled trial. Diabetologia. 2016;59(5):954-65.
  17. Santilli F, Simeone PG, Guagnano MT, Leo M, Maccarone MT, Di Castelnuovo A, et al.Effects of Liraglutide on Weight Loss, Fat Distribution, and beta-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes. 2017;40(11):1556-64.
  18. Ten Kulve JS, Veltman DJ, van Bloemendaal L, Barkhof F, Drent ML, Diamant M, et al. Liraglutide Reduces CNS Activation in Response to Visual Food Cues Only After Short-term Treatment in Patients With Type 2 Diabetes. Diabetes care. 2016;39(2):214- 21.
  19. Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. N Engl J Med 2017;376(3):254–66.
  20. Mendes NF, et al. TGF-beta1 down-regulation in the mediobasal hypothalamus attenuates hypothalamic inflammation and protects against diet-induced obesity. Metabolism 2018;85:171–82.
  21. Wood J, et al. BDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle. Metabolism 2018;87:113– 22. 22.
  22. AdamsJM, et al.Liraglutide modulates appetite and body weight through glucagonlike peptide 1 receptor-expressing glutamatergic neurons. Diabetes 2018;67 (8):1538–48.
  23. Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity. The New England Journal of Medicine, 2021. DOI 10.1056.
  24. Moreira GV. Liraglutida promove mudança da microbiota intestinal com redução da massa adiposa e da esteatose hepática não alcóolica em dois modelos animais de obesidade. Artigo USP 2017.
  25. Cabral MBCB. Novas perspectivas em esteato-hepatite não alcoólica. Universidade do Porto, 2016.
  26. Carvalho D; Nunes JS; Raposo JF; Medina JL; Castro JJ de; Carrilho F. GLP-1 receptor agonists in type 2 diabetes treatment. Revista Portuguesa de Diabetes . 2016; 11 (4): 154-166.
  27. Di Folco U, Vallecorsa N, Nardone MR, Pantano AL, Tubili C. Effects of semaglutide on cardiovascular risk factors and eating behaviors in type 2 diabetes. Acta Diabetol. 2022 Oct;59(10):1287-1294. doi: 10.1007/s00592-022-01936-6.
  28. Velloso LA; Sande-lee SV de. Disfunção hipotalâmica na obesidade. Scielo. Ago 2012. DOI: 10.1590/S0004-27302012000600001.
  29. Burcelin R; Gourdy P. Harnessing glucagon-like peptide-1 receptor agonists for the pharmacological treatment of overweight and obesity. Obesity Reviews, 2017, v. 18, n. 1, p. 89-98. DOI 10.1111.
  30. JingxinLi; Ke He;Jun Ge;CaixiaLi; Zeng Jing.Efficacy and safety ofthe glucagonlike peptide-1 receptor agonist oral semaglutide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes Research and Clinical Practice, 2021.
  31. Paulo et al. Use of a GLP-1 receptor agonist, semaglutide, as therapy for slimming in obese patients. Brazilian Journal of Surgery and Clinical Research – BJSCR, 2021, v.35, n.1, p 54-59.
  32. Madsbad S. Review of head-to-head comparisons of glucagon-like peptide-1 receptor agonists. Diabetes, obesity and Metabolism, 2015, 18: 317-332.
  33. Chadda KR, Cheng TS, Ong KK. GLP-1 agonists for obesity and type 2 diabetes in children: Systematic review and meta-analysis. Obes Rev. 2021 Jun;22(6):e13177. doi: 10.1111/obr.13177.
  34. Valaiyapathi B; Gower B; Ashraf AP. Pathophysiology of Type 2 Diabetes in Children and Adolescents. Current Diabetes Reviews, 2020, v.16, n.3.
  35. Xue X; Ren Z; Zhang A; Yang Q; Zhang W; Liu F. Efficacy and safety of onceweekly glucagon-like peptide-1 receptor agonists compared with exenatide and liraglutide in type 2 diabetes: a systemic review of randomised controlled trials. The International of Clinical Practice, 2016, 70,8, 649-656. DOI 10.1111.
  36. Zaccardi F MD; Htike ZZ MD; Webb DR PhD; Khunti K PhD; Davies MJ MD. Benefits and Harms of Once-Weekly Glucagon-like Peptide-1 Receptor Agonist Treatments. Annals of Internal Medicine, 2016, v. 164, n. 2.
  37. Costa IG; Almeida JD de; Costa KM da; Jardim LFS; Rosa MJ dos santos; Pifano PP; Oliveira RR de; Silva SO; Lima S da silva; Godoy JT. Use of GLP-1 analogues in treatment of obesity: a narrative review. Brazilian Journal of Health Review, Curitiba, 2021, v.4, n.2, p. 4236-4247.
  38. Karagiannis T; Avgerinos I; Liakos A; Prato SD; Matthews DR; Tsapas A; Bekiari E. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis, 2022, 65:1251-1261. DOI 10.1007.
  39. Silva SS da; Silva SH; Aguiar G; Batista SO; Santos ACM; Bandeira FLC; Alves MT; Silva AGF; Sousa VA de; Rodrigues CN da s.; Silva NC da; Souza LA de; Oliveira TRJ; Cardoso B; Gonçalves JB da s. O papel neuroendócrino no controle da fome e da saciedade e sua relação com a obesidade. Pesquisa, Sociedade e Desenvolvimento , [S.l.] , 2022, v. 11, n. 2, pág. e33311225621. DOI: 10.33448.
  40. Pinto ACFLV; Medeiros filho OB de; Sousa MNA de; Lins HDMN. Use of liraglutide in the medicinal therapeutic approach of non-alcoholic steatohepatitis (NASH). Research, Society e development, 2021, v.10, n.4, e389101018921.

How to Cite

Furlan, G. B., Storto, M. E. B. M., Silva, N. A. M. da, Corrêa, M. M. dos S. A., Oliveira, B. R. de, Ribas Filho, D., & Ribas Neto, D. (2023). Use of GLP-1 analogs in the treatment of obesity: an integrative and systematic review. International Journal of Nutrology, 16(1).