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Review
. 2022 Nov;24(11):867-884.
doi: 10.1007/s11883-022-01062-2. Epub 2022 Aug 31.

GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?

Maurício Reis Pedrosa  1 , Denise Reis Franco  2 , Hannah Waisberg Gieremek  2 , Camila Maia Vidal  2 , Fernanda Bronzeri  2 , Alexia de Cassia Rocha  2 , Luis Gabriel de Carvalho Cara  2 , Sofia Lenzi Fogo  2 , Freddy Goldberg Eliaschewitz  2
Affiliations
Review

GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?

Maurício Reis Pedrosa et al. Curr Atheroscler Rep. 2022 Nov.

Abstract

Purpose of review: To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk.

Recent findings: Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3 mg/day liraglutide program and the STEP 2.4 mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.

Keywords: Fat; GLP-1; Glucagon-like peptide 1; Liraglutide; Obesity; Semaglutide; Tirzepatide.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
    1. Klein S, Gastaldelli A, Yki-Järvinen H, Scherer PE. Why does obesity cause diabetes? Cell Metab. 2022;34(1):11–20. https://doi.org/10.1016/j.cmet.2021.12.012 . Recent article on adipose tissue function in obesity. - DOI - PubMed
    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(9765):557–67. https://doi.org/10.1016/S0140-6736(10)62037-5 . - DOI - PubMed - PMC
    1. GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, 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 . - DOI
    1. Gastaldelli A, Abdul Ghani M, DeFronzo RA. Adaptation of insulin clearance to metabolic demand is a key determinant of glucose tolerance. Diabetes. 2021;70(2):377–85. https://doi.org/10.2337/db19-1152 . - DOI - PubMed
    1. Smith GI, Mittendorfer B, Klein S. Metabolically healthy obesity: facts and fantasies. J Clin Invest. 2019;129(10):3978–89. https://doi.org/10.1172/JCI129186 . - DOI - PubMed - PMC

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