JOURNAL ARTICLE
REVIEW

Dipeptidyl peptidase IV inhibitors and the incretin system in type 2 diabetes mellitus

Alissa K Langley, Terri J Suffoletta, Heath R Jennings
Pharmacotherapy 2007, 27 (8): 1163-80
17655515
As understanding of type 2 diabetes mellitus pathophysiology expands, treatments continue to evolve and new pharmacologic targets emerge. Patients with type 2 diabetes exhibit deficiencies of the incretin system; thus, methods for increasing insulinotropic hormones have become a popular target for therapy. A new class of oral antidiabetics has emerged-the dipeptidyl peptidase IV (DPP-IV) inhibitors. Unlike conventional oral antidiabetic agents, these agents promote glucose homeostasis through inhibition of DPP-IV, the enzyme responsible for degradation of two key glucoregulatory hormones: glucagon-like peptide-1 (GLP-1), which extends the action of insulin while also suppressing the release of glucagon, and glucose-dependent insulinotropic peptide (GIP). Other proposed mechanisms of action of GLP-1 and thus DPP-IV inhibitors include satiety, increased beta-cell production, and inhibition of apoptosis of beta cells. Clinical studies have evaluated the potential for DPP-IV inhibition to reduce glucagon levels, delay gastric emptying, and stimulate insulin release. The DPP-IV inhibitors appear to have excellent therapeutic potential in the management of type 2 diabetes as monotherapy or in combination with existing agents, such as metformin. Their pharmacokinetic and pharmacodynamic profiles support once-daily dosing, with sustainable reductions in glycosylated hemoglobin levels and relatively few adverse effects. Their distinctive mechanism of action and adverse-event profiles may offer advantages over existing therapies, including low risk for hypoglycemia and possible augmentation of pancreatic beta-cell regeneration.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
17655515
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"