“GLP-1R Agonists for the Treatment of Obesity: a Patent Review (2015–present)”, 2020-09-11 ():
Background: Glucagon-like peptide-1 (GLP-1) is an endogenous peptide which is secreted by enteroendocrine L cells, GLP-1 receptor agonists (GLP-1 RAs) can exhibit glucoregulation by stimulating insulin release, promote satiety, delay gastric emptying, and reduce energy intake. Liraglutide is the only GLP-1 RA approved for the treatment of obesity. The phase III clinical study of semaglutide has completed and the result showed substantial weight loss effect. GLP-1 RAs have been proven to be safe and effective in clinical trials, they are considered to be promising anti-obesity drugs.
Areas Covered: This review provides an overview of recently published patents describing modified GLP-1 RAs, multi-agonists in the treatment or prevention of obesity from January 2015 to April 2020. Moreover, small molecule GLP-1 RAs, recombinant fusion proteins, combination of GLP-1 RAs with other drugs and the preparation of GLP-1 RAs are also covered.
Expert Opinion: Currently, research on anti-obesity effect of modified GLP-1 RAs has grown substantially, liraglutide accounts for ~56% of the global obesity drug market. Long-acting analogues and multifunctional peptides showed good weight loss activity. As more and more clinical trials are carried out, we believe that GLP-1 RAs will occupy an important position in the market of obesity treatment.
[Keywords: Glucagon-like peptide-1 receptor agonists, obesity, glucagon, glucose-dependent insulinotropic polypeptide]
Since the first GLP-1 receptor agonist liraglutide was approved in 2014 for the treatment of obesity, semaglutide has just completed its first phase III clinical trials with substantially weight loss effect during 68 weeks treatment, GLP-1 receptor agonists are considered to be promising to be the new choice for the overweight people.
Some new strategies are tried to improve patient compliance and convenience, including the multi-agonists, combination of GLP-1RAs with other drugs, and oral preparation of the peptides. We reviewed patents relate to all above mentioned strategies as well as the traditional approaches used in the development of GLP-1 receptor agonists in this article.
Small molecular GLP-1 receptor agonists showed excellent in vitro agonistic activity, but the development of these molecules has not received widespread attention, may be the in vivo effect is not so ideal.
As the first oral preparation of GLP-1 receptor agonists semaglutide was approved in 2019, patents relate to the oral preparation or the controlled-release system have been increasingly applied, and the development of oral peptide preparation will increase in the future.