Semaglutide (trade name Ozempic) is a pharmaceutical drug in development by a Danish company Novo Nordisk for the treatment of type 2 diabetes. Semaglutide is a once-daily glucagon-like peptide-1 analog that differs to others by the presence of an acyl group with a steric diacid at Lys26 and a large synthetic spacer and modified by the presence of a α-aminobutyric acid in position 8 which gives stability against the dipeptidylpeptidase-4. Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors. The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.

Lixisenatide (trade name Adlyxin) is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Liraglutide is an acylated human Glucagon-Like Peptide-1 (GLP-1) receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1. Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membranebound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells. Liraglutide increases intracellular cyclic AMP (cAMP) leading to insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. Liraglutide also decreases glucagon secretion in a glucose-dependent manner. The mechanism of blood glucose lowering also involves a delay in gastric emptying. GLP-1(7-37) has a half-life of 1.5-2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once daily administration, is a result of self-association that delays absorption, plasma protein binding and stability against metabolic degradation by DPP-IV and NEP. Liraglutide, a subcutaneous, once-daily GLP-1 agonist, is approved for the treatment of type 2 diabetes in the United States and Europe. It also has been studied for weight loss. Liraglutide helps to induce and sustain weight loss in patients with obesity. Its efficacy is comparable to other available agents but it offers the unique benefit of improved glycemic control.

Exenatide (exendin-4) is sold under the brand name BYETTA to improve glycemic control in people with type 2 diabetes mellitus. Exenatide is a glucagon-like peptide 1 (GLP-1) receptor agonist that enhances glucose-dependent insulin secretion by the pancreatic beta cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals but does not interfere with glucagon release in response to hypoglycemia.