Glucagon-like peptide 1 (GLP-1)

Glucagon-like peptide 1 (GLP-1) at Bachem

Glucagon-like peptide 1 (GLP-1) is a hormone that enhances insulin secretion and shares similarities with glucagon. GLP-1 has beneficial effects on the pancreas, brain, and stomach. It promotes insulin release, increases insulin-producing cells, reduces glucagon secretion, and has even shown additional benefits in reducing the risk of cardiac problems.


What is glucagon-like peptide 1?

Glucagon-like peptide 1 belongs to a family of hormones called incretins because they enhance insulin secretion due to factors derived from the gut. Glucagon-like peptide 1 is a product of a molecule called pre-proglucagon, a polypeptide (i.e., chain of amino acids, which are organic compounds that make up proteins) that is split to produce many hormones, including glucagon. Because they come from the same source, these hormones share some similarities and are called “glucagon-like”. Cells found in the lining of the small intestine (called L-cells) are the primary source of glucagon-like peptide 1, although the pancreas and the central nervous system both secrete it, albeit in lower amounts. Incretins have a short half-life and quick renal clearance naturally, so incretin memetics such as GLP-1 analogues and receptor agonists have been developed that exhibit better pharmacokinetic properties.


How do glucagon-like peptide-1 receptor agonists (GLP-1RAs) work, and what are they used for?

Receptor agonists (RA) are molecules that activate a specific receptor and trigger a response. Agonists can be natural ligands or synthetic drugs mimicking a natural ligand of the targeted receptor. There are many beneficial effects of activating GLP-1 receptors, with the three main impacts of GLP-1RAs being on the pancreas, the brain, and the stomach.

  • In the pancreas, GLP-1 receptor activation encourages the release of insulin, increases the volume of cells within the pancreas that produce insulin (beta cells), and reduces the release of glucagon.
  • In the brain, GLP-1RAs act on the appetite centers, increasing the feeling of fullness between and during meals.
  • In the stomach, GLP-1RAs increase the time until the stomach empties itself.

The GLP-1 receptor agonists are successful in the treatment of type-2 diabetes and the treatment of obesity, with a variety of additional benefits currently being explored.


What are the other effects of GLP-1 receptor agonists?

Together with promoting weight loss and blood sugar regulation, GLP-1RAs seem to have other significant benefits. According to research, various medications in these classes may reduce the risk of cardiac problems, such as:

  • heart failure
  • stroke
  • kidney disease

People taking these drugs have seen improved blood pressure and cholesterol levels. Whether these benefits are from the drug or the weight loss is still studied.
One of the downsides to GLP-1RA drugs is the ease of administration. Currently, all but one registered drug have to be administered with an injection. And, like with any drug, there are some risks and side effects.


List of commercial GLP-1 agonist sorted by peptide name

PeptideBrand nameOriginal ManufacturerFDA Approval forOther indicationsFDA Approval Date
Dulaglutide Trulicity®Eli Lilly and Companytype 2 diabetes 2014/2020
ExenatideByetta®AstraZeneca type 2 diabetes2005
Exenatide extended-releaseBydureon
AstraZenecatype 2 diabetes2005
Liraglutide Saxenda®Novo Nordiskweight-loss2010
LiraglutideVictoza®Novo Nordisktype 2 diabetesweight-loss2010
Lixisenatide Adlyxin®
Sanofitype 2 diabetes2016
Semaglutide Ozempic® Novo Nordisktype 2 diabetesweight-loss2017
Semaglutide Wegovy®Novo Nordiskweight-loss2017
SemaglutideRybelsus® Novo Nordisktype 2 diabetesweight-loss2019
Tirzepatide Mounjaro®Eli Lilly and Companytype 2 diabetesweight-loss2022

GLP-1RA manufacturer Bachem

As a CDMO, Bachem develops and produces several GLP-1RAs for the generic market. Generic API development and manufacturing involves more than just following a few simple steps. The assistance and services offered around the molecules are essential. Our partners and clients rely on the passion and knowledge to provide all the ingredients for a positive API supply experience and successful launch, as well as to make generics available and affordable for patients around the world. Going above and above makes you stand out in the crowded generics market. As a customer, you can concentrate on creating your masterpiece while CDMOs like Bachem handle the rest!

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What is Exenatide?

Exenatide is a glucagon-like peptide-1 (GLP-1) analog. To improve glycemic control, it activates the GLP-1 receptor, which leads to an increase in insulin secretion, a decrease in glucagon production, and a slowing of stomach emptying. In 2005, the FDA approved exenatide. It comes in formulations for both immediate and sustained release.


What is Liraglutide?

Liraglutide is a GLP-1 analogue with the lysine residue at position 20 conjugated on the side chain by a fatty acid via a glutamic spacer and the lysine amino acid at position 27 replaced by an arginine. Due to the presence of the fatty acid side-chain, liraglutide has a prolonged half-life in the body than GLP-1, which enables an efficient weight loss and glycemic management. Liraglutide is prescribed as a supplement to diet and exercise to help persons with type 2 diabetes mellitus regulate their blood sugar levels. Liraglutide was approved for medical use in the European Union in 2009.

What is Lixisenatide?

The glucagon-like peptide-1 (GLP-1) receptor agonist called lixisenatide is used to treat type II diabetes. The adenylyl cyclase is activated when lixisenatide reacts with the GLP-1 receptor.  It stimulates insulin production by activating the amplification pathway . Sanofi sells it in the US under the brand name Adlyxin and in the EU under the name Lyxumia. The drug was approved by the FDA in 2016.


What is Dulaglutide?

Dulaglutide is a GLP-1 receptor agonist consisting of GLP-1(7-37). In the management of type 2 diabetes, it has been approved as an adjuvant therapy to diet and exercise. In February 2020, the FDA approved the use of dulaglutide in patients with type 2 diabetes and various cardiovascular risk factors in order to prevent cardiovascular events. The drug had previously been approved by the FDA in 2014.


What is Semaglutide?

Semaglutide is a synthetic lipopeptide (peptide conjugated with a fatty acid chain similar to liraglutide) with a linear sequence of 31 amino acids. It is used to treat type 2 diabetes as a GLP-1 receptor agonist. It also functions as an appetite suppressant, an anti-obesity medication, a hypoglycemic agent, and as a neuroprotective agent. Semaglutide exists both as injectable as well as oral drug and was first approved in 2017.


What is Tirzepatide?

Tirzepatide is a dual GLP-1 receptor agonist and GIP (glucose-dependent insulinotropic polypeptide) used for the treatment of type 2 diabetes to supplement diet and exercise. It is a 39-amino acid linear lipopeptide that is conjugated to a C20 fatty diacid moiety via a linker that is connected to lysine-20. It has a role as a glucagon-like peptide-1 receptor and gastric inhibitory polypeptide receptor agonist, as an anti-obesity and hypoglycemic agent. Tirzepartide was approved in the US and EU in 2022.


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