GLP-1 agonists were initially developed for type 2 diabetes. The 2022 American Diabetes Association standards of medical care recommend GLP-1 agonists as a first line therapy for type 2 diabetes, specifically in patients with atherosclerotic cardiovascular disease or obesity. The GLP-1 RA drugs were also noted to reduce food intake and body weight significantly, and some have also been approved to treat obesity in the absence of diabetes. They are also in development for other indications, such as non-alcoholic fatty liver disease, polycystic ovary syndrome, and diseases of the reward system such as addictions.
The development of GLP-1 receptor agonists (GLP-1 RAs) has evolved over several decades, marked by significant milestones in diabetes treatment and advancements in understanding the role of glucagon-like peptide-1 (GLP-1) in glucose homeostasis. Here is a simplified chronological history of key developments in GLP-1 RA drugs from their inception to the present:
The 1980s marked the discovery of GLP-1 and its role in glucose metabolism. Researchers identified GLP-1 as a hormone secreted by the intestine in response to food intake. The subsequent discovery of GLP-1 receptors paved the way for the development of drugs targeting these receptors.
Exenatide, the first GLP-1 RA, was approved by the U.S. Food and Drug Administration (FDA) in 2005. Developed by Amylin Pharmaceuticals, it is an injectable medication that enhances insulin secretion and suppresses glucagon release, leading to improved blood sugar control.
Liraglutide, developed by Novo Nordisk, gained FDA approval in 2010. It is a once-daily injectable GLP-1 RA that improves glycemic control and promotes weight loss. Liraglutide demonstrated cardiovascular benefits in subsequent trials.
A long-acting formulation of exenatide, Bydureon, received FDA approval in 2012. It is administered weekly and provides sustained GLP-1 receptor activation.
Both dulaglutide (Eli Lilly) and albiglutide (GlaxoSmithKline) gained FDA approval in 2014. These once-weekly injectables provide convenient dosing options for patients.
Lixisenatide, developed by Sanofi, received FDA approval in 2016. It is indicated for once-daily injection and is used in conjunction with diet and exercise for improved glycemic control.
Semaglutide, a long-acting GLP-1 RA developed by Novo Nordisk, was approved by the FDA in 2017. Administered once weekly, it has demonstrated efficacy in reducing cardiovascular events.
In 2019, oral semaglutide (Rybelsus) became the first oral GLP-1 RA approved by the FDA. It provides an alternative to injectable formulations, offering convenience for patients. Rybelus was developed by Novo Nordisk of Sweden.
In 2021, semaglutide (Wegovy) received FDA approval for Novo Nordisk’s new drug for chronic weight management in adults with obesity or overweight and at least one weight-related condition. While primarily indicated for weight loss, its approval marks another milestone in the use of GLP-1 RAs.
Mounjaro (tirzepatide) an Eli Lilly medicine was approved for the treatment of diabetes.
Zepbound (tirzepatide) an Eli Lilly medicine was approved by the FDA for the treatment of obesity.