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Liraglutide (Victoza, Saxenda), which is FDA approved in diabetes and obesity, currently has the most evidence

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Keywords: glucagon-like peptide-1 receptor agonist (GLP-1RA), incretin based therapy, glucose-depent insulinotropic peptide (GIP), dual agonists, tirzepatide, type 2 diabetes Introduction Recent data from the International Diabetes Foundation (IDF) Diabetes World Atlas released at the end of 2021 shows a consistently rising prevalence of type 2 diabetes (T2D) with different incidence increases in various regions of the world

Several methods are introduced to increase the half-life of GLP-1 including: (i) modifying peptides to make them resistant to cleavage by DPP-4, such as exenatide twice daily and lixisenatide, (ii) attaching free fatty acid side chains to liraglutide and semaglutide, which enhances their binding to plasma albumin thereby preventing renal filtration of GLP-1 and prolonging their action in vivo [36, 37], (iii) conjugation of albumin or the Fc fragment of IgG to GLP-1 molecule is used in albiglutide and dulaglutide [37, 38], (iv) development of modified nanoparticles for the controlled release of exenatide-LAR (long-acting release) that provide prolonged release of the peptide [39], and finally, (v) chemical permeation enhancers such as sodium salcaprozate (SNAC) could be utilized to overcome the low permeability and high enzymatic degradation of the gastrointestinal tract of GLP-1 analog that is administrated orally such as semaglutide [40]