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DPP-4 Inhibition

A means to enhance intact incretins

After release, GLP-1 (7-36) and GIP (1-42) are rapidly metabolized by the enzyme DPP-4, 13,27 which is located in various tissues, on the capillary surfaces, and in soluble form in the circulation. 38

DPP-4 cleaves off the first 2 amino acids from the intact peptides, producing 2 truncated peptides, GLP-1 (9-36) and GIP (3-42), 13,25,39 which are mainly eliminated through the kidneys. 28,40

These truncated peptides do not activate the respective GLP-1 or GIP receptors in the pancreatic alpha and beta cells 40 and do not affect insulin release or glucose control. 38,41

DPP-4 inhibition has been shown to slow the degradation of GLP-1 and GIP to their truncated forms, therefore prolonging the survival of intact GLP-1 and GIP and their effects on glucose regulation. 13,14,15

dpp-4 inhibitor

Important Information About JANUMET and JANUVIA
JANUMET is indicated, as an adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both sitagliptin and metformin is appropriate.

JANUVIA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

JANUMET / JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

JANUMET / JANUVIA have not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUMET / JANUVIA.

Before prescribing JANUMET, please read the Prescribing Information, including the Boxed Warning about lactic acidosis. The Medication Guide also is available.
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Vahl TP, Paty BW, Fuller BD, et al. Effects of GLP-1-(736)NH2, GLP-1-(737), and GLP-1-(936)NH2 on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans. J Clin Endocrinol Metab. 2003;88:17721779.
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