Glucagon-Like Peptide 1 Therapy: From Discovery to Type 2 Diabetes and Beyond

Abstract

The therapeutic benefits of the incretin hormone, glucagon-like peptide 1 (GLP1), for people with type 2 diabetes and/or obesity, are now firmly established. The evidence-base arising from head-to-head comparative effectiveness studies in people with type 2 diabetes, as well as the recommendations by professional guidelines suggest that GLP1 receptor agonists should replace more traditional treatment options such as sulfonylureas and dipeptidyl-peptidase 4 (DPP4) inhibitors. Furthermore, their benefits in reducing cardiovascular events in people with type 2 diabetes beyond improvements in glycaemic control has led to numerous clinical trials seeking to translate this benefit beyond type 2 diabetes. Following early trial results their therapeutic benefit is currently being tested in other conditions including fatty liver disease, kidney disease, and Alzheimer's disease.

The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update

“…Liraglutide was the first GLP-1 receptor analogue approved for the management of obesity, thus starting the new era of gastrointestinal peptide agonist pharmacotherapy for the treatment of both diabetes and obesity. Recent comprehensive reviews of the many GLP-1 agonists that have come to the market in the last 20 years have been published elsewhere [ 8 , 37 ]. There have been several head-to-head clinical trials comparing the efficacy of different GLP-1 receptor agonists broadly demonstrating the superiority of semaglutide to comparators [ 37 ].…”

“…Recent comprehensive reviews of the many GLP-1 agonists that have come to the market in the last 20 years have been published elsewhere [ 8 , 37 ]. There have been several head-to-head clinical trials comparing the efficacy of different GLP-1 receptor agonists broadly demonstrating the superiority of semaglutide to comparators [ 37 ]. Since then, the Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) cardiovascular outcomes trial has shown that semaglutide 2.4 mg once weekly was associated with a significant 20% relative risk reduction in major cardiovascular adverse events compared with placebo [ 38 ].…”