Function of dulaglutide in type 2 diabetes
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Function of dulaglutide in type 2 diabetes



Dulaglutide, sold under the brand name Trulicity, is a GLP-1 receptor agonist which is a class of medications that play the same role as GLP-1 by binding to its receptor, and can have therapeutic benefit for patients with type 2 diabetes. GLP-1 receptor agonists, also known as incretin mimetics have an advantage over older insulin secretagogues with a lower risk of inducing hypoglycemia. Dulaglutide consists of a GLP-1(7-37) analogue linked to a human lgG4-Fc heavy chain by a small peptide linker.

Pharmacologic action

Type 2 diabetes is due to the insulin resistance of some pancreatic beta cells, leading to insufficient insulin production and inappropriately releasing of glucose form liver into the blood. GLP-1, as an incretin, is expressed by glucagon gene in the L cells of intestinal mucosa and has two biological active forms, namely GLP-1(7-36) and GLP-1(7-37) amide. Since the lack of incretin or increased breakdown of GLP-1 are both associated with type 2 diabetes, dulaglutide, as an agonist of DLP-1 receptors, increases intracellular cAMP of islet beta cells and leads to insulin production. Dulaglutide, consisting of GLP-1(7-37) analogue, can promote insulin gene transcription, insulin synthesis and secretion, increasethe number of islet beta cells by binding to GLP-1 receptors on the surface of islet beta cells and strongly inhibit the release of glucagon by acting on islet alpha cells.


Once dulaglutide binds to GLP-1 receptors, it can stimulate islet beta cells proliferation and differentiation, prevent its apoptosis so that increase the number of insulin secretion cells and enhance their abilities of insulin secretion. Additionally, dulaglutide has the effect of decreasing the production of glucagon by islet alpha cells, which is helpful for the situation of insufficient insulin relatively. Compared to the older insulin secretagogues for the treatment of type 2 diabetes such as sulfonylures or meglitinides, dulaglutide has a lower risk of conducing hypoglycemia because the increased insulin release caused by dulaglutide is glucose-dependent. Dulaglutide also slows the gastric emptying.

Pharmacokinetics and metabolism

After a subcutaneous administration of dulaglutide at a steady state, the plasma concentration achieves its maximum in 24 to 72 hours. With the subcutaneous injection administrated of 0.75mg and 1.5mg dulaglutide to a steady state, the mean clearance is about 0.111L/h for the 0.75mg dose, and 0.107L/h for the 1.5mg dose, while the volume of distribution is 19.2L (range from 14.3 to 26.4) and 17.4 (range from 9.3 to 33) respectively. Dulaglutide is presumed to be metabolized by general protein catabolism pathways. Its mean elimination half-life is approximately 5 days.


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