B.C.'s Drug and Poison Information Centre.

ACTION A selective inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme. Lowers blood glucose levels by increasing insulin secretion and decreasing hepatic glucose production. Enhances the glucose-stimulated insulin secretion response to GLP-1 and GIP, which are released when food in the GI tract raises blood glucose levels above 3.05 mmol/L (55mg/dL). GLP-1 and GIP are incretin (INtestinal seCRETion of INsulin) peptides that lower blood glucose levels by stimulating insulin release from pancreatic beta cells. Patients with Type 2 diabetes mellitus (T2DM) have an impaired GLP-1 and GIP response to food and less insulin secretion. In diabetes, saxagliptin increases the amount of active GLP-1 by 2to 3-fold by inhibiting the enzyme that rapidly inactivates it, DPP-4. Enhanced GLP-1 also reduces glucagon secretion which leads to less hepatic glucose production. The postprandial glucose excursion (increase) after a meal is reduced by this drug in patients with T2DM. In mice, beta cell mass and function have been enhanced by DPP-4 inhibitors, but there is no evidence at present of a change in the progressive loss of pancreatic insulin secretion observed in humans with T2DM. GLP-1 also decreases gastric emptying and appetite but these effects are not usually seen with DPP-4 inhibitors and there is usually a neutral effect on weight.