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The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.
Combination GLP-1/glucagon receptor agonists provide the thermogenic benefits of glucagon activation while almost eliminating hyperglycemia induced by glucagon receptor activation. Several such drugs have reached human trials for obesity, diabetes, and non-alcoholic fatty liver disease but adverse effects have hampered development.
Different GLP-1 receptor agonists go through inactivation by dipeptidyl peptidase-4 (DPP-4) enzymes (The clinical use of GLP-1 is hampered by its short-half life in the circulation (1-2 min), because of its proteolytic degradation by the enzymes dipeptidyl peptidase-4 (DPP-4) and neutral endopeptidase).
GLP-1 drugs like Ozempic, Mounjaro, Wegovy, and Zepbound are powerful tools for treating diabetes and aiding with weight loss, but a new study suggests these medications could also help prevent ...
Native GLP-1 is a peptide hormone with a half-life of two minutes because it is rapidly cleared by the enzyme dipeptidyl peptidase-4. [29] As a result, different GLP-1 agonist drugs are modified in various ways to extend the half-life, resulting in drugs that can be dosed multiple times per day, daily, weekly, or less often. [29]
Between Novo Nordisk's slightly disappointing results for its latest GLP-1 candidate, CagriSema, and questions that remain about Amgen's highly anticipated once-monthly injectable, MariTide, some ...
Exenatide (also Exendin-4, marketed as Byetta) is the first GLP-1 agonist approved for the treatment of type 2 diabetes. Exenatide is not an analogue of GLP but rather a GLP agonist. [32] [33] Exenatide has only 53% homology with GLP, which increases its resistance to degradation by DPP-4 and extends its half-life. [34]
GLP-1 medications are best if taken long-term, but shortages, price, and side effects like GI discomfort are potential barriers for some. Additionally, other medical issues may hamper weight loss.