JOURNAL ARTICLE
REVIEW

Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes

Carolyn F Deacon, Jens J Holst
Advances in Therapy 2009, 26 (5): 488-99
19444391
Saxagliptin is a potent and selective reversible inhibitor of dipeptidyl peptidase-4, which is being developed for the treatment of type 2 diabetes. It is absorbed rapidly after oral administration and has a pharmacokinetic profile compatible with once daily dosing. Saxagliptin is metabolized in vivo to form an active metabolite, and both parent drug and metabolite are excreted primarily via the kidneys. Saxagliptin reduces the degradation of the incretin hormone glucagon-like peptide-1, thereby enhancing its actions, and is associated with improved beta-cell function and suppression of glucagon secretion. Clinical trials of up to 24 weeks duration have shown that saxagliptin improves glycemic control in monotherapy and provides additional efficacy when used in combination with other oral antidiabetic agents (metformin, sulfonylurea, thiazolidinedione). Both fasting and postprandial glucose concentrations are reduce leading to clinically meaningful reductions in glycated hemoglobin, and due to the glucose-dependency of its mechanism of action, there is a low risk of hypoglycemia. Saxagliptin is reported to be well tolerated with a side-effect profile similar to placebo. It has a neutral effect on body weight and dose adjustment because of age, gender, or hepatic impairment is not necessary. Saxagliptin is being co-developed by Bristol-Myers-Squibb (New York, NY, USA) and AstraZeneca (Cheshire, UK), and is currently undergoing regulatory review.

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