The ground-breaking development of the incretin agonists by manipulation of the incretin system,including the gut hormones glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide(GIP),as well as...The ground-breaking development of the incretin agonists by manipulation of the incretin system,including the gut hormones glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide(GIP),as well as the pancreatic hor-mone glucagon,has led to the emergence of promising pharmacotherapy for metabolic health.The GLP-1 receptor agonists(GLP-1RAs),namely liraglutide,dulaglutide,albiglutide,exenatide,and semaglutide,have been found to have beneficial effects on glycated hemoglobin,weight,lipid profile,and liver fat and thereby improving cardiometabolic health.Other drugs of the same group in development include Orforglipron,which has a high weight loss efficacy(-15%weight reduction).Long-acting GLP-1RAs in trials are Ecnoglutide,Efpeglenatide,TG103,and Visepegenatide.Many of these have cardiovascular benefits in terms of reduction in MACE(Non-fatal MI,Non-fatal stroke,and mortality).Tirzepatide is a dual GIP/GLP-1RA,the first drug of the group to be approved for diabetes and obesity with remarkably lower gastrointestinal side effects compared to GLP-1 monoagonists.The dual GLP-1/glucagon co-agonists cause tremendous weight loss due to the synergistic action.Most drugs in this class are long-acting and developed for once-weekly administration.The revolutionary triple agonists at the GLP-1,GIP,and Glucagon receptors have demonstrated the highest achievable weight loss with pharmaco-therapy.Retatrutide and Efocipegtrutide belong to this novel group of drugs.The newer drugs in the broad category of incretin co-agonists include the GLP-1/amylin receptor agonist like CagriSema and Amycretin,oral GLP-1 agonists other than semaglutide,and the peptide YY/GLP-1 receptor dual agonists.The profound bioche-mical and weight loss outcomes associated with incretin co-/poly-agonists are expected to translate into outstanding cardiometabolic benefits,the theme of this evidence review.展开更多
文摘The ground-breaking development of the incretin agonists by manipulation of the incretin system,including the gut hormones glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide(GIP),as well as the pancreatic hor-mone glucagon,has led to the emergence of promising pharmacotherapy for metabolic health.The GLP-1 receptor agonists(GLP-1RAs),namely liraglutide,dulaglutide,albiglutide,exenatide,and semaglutide,have been found to have beneficial effects on glycated hemoglobin,weight,lipid profile,and liver fat and thereby improving cardiometabolic health.Other drugs of the same group in development include Orforglipron,which has a high weight loss efficacy(-15%weight reduction).Long-acting GLP-1RAs in trials are Ecnoglutide,Efpeglenatide,TG103,and Visepegenatide.Many of these have cardiovascular benefits in terms of reduction in MACE(Non-fatal MI,Non-fatal stroke,and mortality).Tirzepatide is a dual GIP/GLP-1RA,the first drug of the group to be approved for diabetes and obesity with remarkably lower gastrointestinal side effects compared to GLP-1 monoagonists.The dual GLP-1/glucagon co-agonists cause tremendous weight loss due to the synergistic action.Most drugs in this class are long-acting and developed for once-weekly administration.The revolutionary triple agonists at the GLP-1,GIP,and Glucagon receptors have demonstrated the highest achievable weight loss with pharmaco-therapy.Retatrutide and Efocipegtrutide belong to this novel group of drugs.The newer drugs in the broad category of incretin co-agonists include the GLP-1/amylin receptor agonist like CagriSema and Amycretin,oral GLP-1 agonists other than semaglutide,and the peptide YY/GLP-1 receptor dual agonists.The profound bioche-mical and weight loss outcomes associated with incretin co-/poly-agonists are expected to translate into outstanding cardiometabolic benefits,the theme of this evidence review.
