The glucagon-like peptide-1(GLP-1)drugs poised to conquer obesity
Obesity has become a global public health issue,with the number of overweight/obese individuals increasing annually.However,weight loss faces various difficulties and challenges.Incretin medications,represented by glucagon-like peptide-1(GLP-1),have brought new hope in the battle against obesity.As a result,GLP-1 was recognized as the top scientific breakthrough of 2023.Since its isolation and identification in 1983,GLP-1 has been increasingly gaining attention for its clinical applications.Exendin-4 is the first GLP-1 receptor agonist(GLP-1RA)approved for market by the U.S.Food and Drug Administration(FDA).Subsequently,the development of GLP-1 RAs has entered the fast track.Liraglutide,dulaglutide,semaglutide,and other GLP-1 receptor agonists(GLP-1 RAs)have been successively developed and approved for market.Initially introduced as antidiabetic agents,further research revealed the positive impact of GLP-1 RAs on conditions such as obesity,cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).As scientific exploration into GLP-1 deepens,researchers have begun to investigate broader therapeutic pathways,with a particular focus on the development of multi-receptor agonists.The 2023 Banting Scientific Achievement Award was conferred upon Dr.Matthias H.Tschop,dedicated to multi-receptor agonist research.Dr.Tschop's team proposed an efficient weight-loss strategy by simultaneously targeting multiple gut hormone receptors,such as GLP-1 R,GIPR,and GCGR,to harness synergistic effects.GLP-1 RA-based single-target and multi-target combination drugs are a new generation of treatment for obesity and diabetes,and their weight loss is close to that of bariatric surgery,and may be effective in preventing type 2 diabetes mellitus,and a variety of dual-and triple-receptor agonists are currently under development.However,the long-term practice and application of such drugs for obesity control still need to be further considered.In summary,the results of GLP-1 studies in the fields of type 2 diabetes mellitus,obesity,and cardiovascular diseases demonstrate excellent therapeutic potential.With the in-depth study of its mechanism and the continuous upgrading of technical methods,GLP-1 is expected to make new breakthroughs in many aspects.Firstly,future studies may explore the application of GLP-1 in neurodegenerative diseases,oncology,nonalcoholic fatty liver disease,and other fields.Secondly,GLP-1RA has greatly improved the convenience of patient treatment from daily to weekly preparations,from injection preparations to oral peptide preparations,and then to small molecule oral preparations,and GLP-1 preparations will become more diversified in the future to meet the individualized needs of patients.In addition,the in-depth exploration of multi-receptor agonists will lead to more efficient and comprehensive treatment options,providing more benefits to patients.
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