Dipeptidyl peptidase-4 inhibitors

Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors or gliptins) are a class of oral hypoglycemics that block Dipeptidyl peptidase-4 (DPP-4), an enzyme responsible for the inactivation of incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones are involved in the regulation of blood glucose levels. By inhibiting DPP-4, gliptins increase the levels of active incretin hormones, which in turn increases insulin secretion and decreases glucagon secretion. This action is glucose-dependent, which means it diminishes the risk of hypoglycemia when compared to other antidiabetic drugs.

Mechanism of Action

DPP-4 inhibitors work by blocking the action of the DPP-4 enzyme, which is responsible for breaking down incretin hormones. Incretin hormones, primarily GLP-1 and GIP, play a crucial role in glucose metabolism by enhancing insulin secretion in response to meals and suppressing glucagon secretion. By preventing the degradation of incretin hormones, DPP-4 inhibitors allow these hormones to remain active in the body for a longer period, thus improving the regulation of blood glucose levels.

Clinical Use

DPP-4 inhibitors are used in the treatment of Type 2 diabetes as they help in managing blood glucose levels without causing significant weight gain or hypoglycemia. They are often prescribed as part of a combination therapy with other antidiabetic medications, such as metformin or sulfonylureas, to achieve better glycemic control.

Adverse Effects

While DPP-4 inhibitors are generally well tolerated, they can cause some side effects, including nasopharyngitis, headache, and upper respiratory tract infections. There is also a concern about the potential risk of pancreatitis and arthralgia associated with their use, although the evidence is mixed.

Examples

Some common DPP-4 inhibitors include:

• Sitagliptin (Januvia)
• Vildagliptin (Galvus)
• Saxagliptin (Onglyza)
• Linagliptin (Tradjenta)
• Alogliptin (Nesina)

Comparison with Other Antidiabetic Drugs

DPP-4 inhibitors have a unique mechanism of action compared to other antidiabetic drugs. Unlike sulfonylureas and insulin, which can cause hypoglycemia and weight gain, DPP-4 inhibitors have a lower risk of these side effects. However, they may not be as effective in reducing blood glucose levels as some other medications.

Future Directions

Research is ongoing to explore the full potential of DPP-4 inhibitors in diabetes management and to investigate their effects beyond glycemic control, such as on cardiovascular outcomes and beta-cell function.

See Also

• Antidiabetic drug
• Incretin
• Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists)
• Type 2 diabetes management