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The Role Of Dpp 4 Inhibitors In Type 2 Diabetes Mellitus

2600 words - 11 pages

As the incidence of type 2 diabetes is steadily increasing, the demand for treatment options is increasing. Dipeptidyl peptidase-4 inhibitors (DPP-4) are a new class of oral anti-hyperglycemic medications that target the incretin system found in the gut. Evidence has shown that treatment with DPP-4 inhibitors has shown significant reductions in HbA1c and increased pancreatic β-cell function without an increased risk of hypoglycemia. In this document, the pharmacology, clinical efficacy, and incidence of adverse effects will be reviewed in an attempt to target a patient population that would benefit the most from treatment with DPP-4 inhibitors.
The role of DPP-4 inhibitors in type 2 diabetes mellitus management
INTRODUCTION
Type 2 diabetes mellitus is a chronic, progressive disease that currently affects approximately 285 million people worldwide and is estimated to affect 430 million people by 2030.1 As the numbers increase, the demand for effective treatments also increases. In addition to lifestyle modifications, the current recommendation for the first-line treatment for people with new-onset type 2 diabetes mellitus is metformin, an oral anti-hyperglycemic agent. In patients who are currently taking metformin but are inadequately controlled, a second oral agent is typically added on. Several second-line oral anti-hyperglycemic agents are available, including older agents such as sulfonlyureas, glinides, thiazolidinediones, α-glucosidase inhibitors, and amylin agonist (pramlintide), as well as newer agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.2 However, the debate on which second-line agent should be used is omnipresent.
In 2006, the first oral DPP-4 inhibitor, sitagliptan, was approved by the Food and Drug Administration for use in combination with metformin and thiazolidinediones as well as use as monotherapy. These agents embody an entirely new approach to the treatment of patients with type 2 diabetes mellitus by targeting the incretin system.2,3
MECHANISM OF ACTION
Overview of the incretin system
Incretins are hormones found throughout the intestines that are released in response to ingestion of a meal and decreased in fasting states. Two specific incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), play a major role in the regulation of glucose homeostasis. GIP is released from K cells found in the duodenum and small intestine in response to the ingestion of fats, while GLP-1 is secreted by L cells when any nutrients are present at any location in the gut. Once GIP and GLP-1 are secreted, they bind to receptors found in several locations in the human body, including the stomach, liver, adipose tissue, and pancreatic islet cells.3,4
Glucose-dependent activation of GLP-1 results in an increase in the amount of insulin produced and released from pancreatic β-cells in response to hyperglycemia. Simultaneously,...

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