GLP-1 receptor agonists for weight loss, benefits and risks: A systematic review of the literatura

Diego Silva Pacheco de Moraes; Marcelo Adrián Estrin

doi:10.59471/ijhsc202555

Authors

Diego Silva Pacheco de Moraes Universidad Abierta Interamericana, Facultad de Medicina y Ciencias de la Salud, Carrera de Medicina. Buenos Aires, Argentina Author
Marcelo Adrián Estrin Universidad Abierta Interamericana, Facultad de Medicina y Ciencias de la Salud, Carrera de Medicina. Buenos Aires, Argentina Author

DOI:

https://doi.org/10.59471/ijhsc202555

Keywords:

GLP-1 agonists, weight loss, risks, evaluation, pharmacovigilance

Abstract

Background: Obesity is a chronic disease linked to numerous complications. A 5-15% reduction in body weight can significantly improve obesity-related complications. Despite the benefits of weight reduction, there are numerous challenges in achieving and maintaining long-term weight loss. Pharmacotherapy offers a means by which individuals with obesity can achieve and sustain the desired weight, thereby reducing the risk of associated complications. The prevalence of obesity in the United States has increased over the past decades, and despite the availability of approved medications for its treatment, individuals with obesity may not be accessing them or receiving treatment at levels commensurate with the prevalence of the disease. Reasons for the low levels of initiation and long-term use may include reluctance to recognize obesity as a disease, lack of reimbursement, healthcare professional inexperience, and misconceptions about the efficacy and safety of available treatments. Objectives: This study focuses on informing primary care medical professionals about the mechanism of action of glucagon-like peptide-1 receptor agonists (GLP- 1RAs) in weight loss and long-term maintenance thereof, as well as on the efficacy and safety of this class of treatment. GLP-1RA therapy, initially developed to treat type 2 diabetes, has proven effective in reducing body weight. The daily subcutaneous administration of liraglutide has been approved, and the weekly subcutaneous administration of semaglutide is being investigated in phase III trials for obesity management. Material and methods: This work adopts a systematic review approach, using biomedical databases to gather relevant evidence on the efficacy and safety of GLP-1RAs in weight management. Studies addressing both initial weight loss and long-term maintenance are analyzed, including considerations on adverse effects and contraindications of different drug classes, to guide decision-making in the pharmacological treatment of obesity.

References

Ma H, Lin YH, Dai LZ, et al. Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis. BMJ Open. 2023;13:e061807. doi:10.1136/bmjopen-2022-061807

Karagiannis T, Avgerinos I, Liakos A, Del Prato S, Matthews DR, Tsapas A, et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Diabetologia. 2022;65(8):1251–61. doi:10.1007/s00125-022-05715-4. PMID: 35579691; PMCID: PMC9112245.

Li H, Yu G, Huang Q, Yang B, Nie J, Liu Y, et al. Efficacy and safety of GLP-1RAs for people with obesity: A systematic review based on RCT and Bayesian network meta-analysis. Biomed Pharmacother. 2024;171:116150. doi:10.1016/j.biopha.2024.116150. PMID: 38242040.

Guo X, Zhou Z, Lyu X, Xu H, Zhu H, Pan H, et al. The Antiobesity Effect and Safety of GLP-1 Receptor Agonist in Overweight/Obese Patients Without Diabetes: A Systematic Review and Meta-Analysis. Horm Metab Res. 2022;54(7):458–71. doi:10.1055/a-1844-1176. PMID: 35512849.

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. doi:10.1186/s12933-023-01765-z. PMID: 36841762; PMCID: PMC9960425.

Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, 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 Randomized Clinical Trial. JAMA. 2021;325(14):1403–13. doi:10.1001/jama.2021.1831. PMID: 33625476; PMCID: PMC7905697.

Cai W, Zhang R, Yao Y, Wu Q, Zhang J. Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials. Front Public Health. 2024;12:1277113. doi:10.3389/fpubh.2024.1277113. PMID: 38356942; PMCID: PMC10864442.

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. doi:10.1056/NEJMoa2032183. PMID: 33567185.

Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, et al. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med. 2023;389(10):877–88. doi:10.1056/NEJMoa2302392. PMID: 37351564.

Silver HJ, Olson D, Mayfield D, Wright P, Nian H, Mashayekhi M, et al. Effect of the glucagon-like peptide-1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes. Diabetes Obes Metab. 2023;25(8):2340–50. doi:10.1111/dom.15113. PMID: 37188932; PMCID: PMC10544709.