Saxagliptin: A Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus

Abstract

The prevalence of type 2 diabetes mellitus is high and growing rapidly. Suboptimal glycemic control provides opportunities for new treatment options to improve the morbidity and mortality of this progressive disease. Saxagliptin, a selective DPP-4 inhibitor, increases endogenous incretin levels and incretin acitivty. In controlled clinical trials saxagliptin reduces both fasting and postprandial glucose and works in monotherapy and in combination with metformin, TZDs and sulfonylureas. Saxagliptin has a very favourable side effect profile and may have other beneficial non-glycemic effects. The authors review the current available evidence for the safety, efficacy and saxagliptin’s place in therapy for type 2 diabetes mellitus. As understanding of the incretin hormones (GLP-1, GIP) expand we may see additional important non-glycemic effects that may affect the chronic management of type 2 diabetes mellitus.

Potential of pharmacological modulation of level and activity of incretins in diabetes mellitus type 2

“…In 24 week clinical trials, saxagliptin monotherapy reduced glycated hemoglobin from 0.4% to 0.9%. The drug had no effect on body weight of patients and did not cause adverse effects in doses ranged from 2.5 mg to 40 mg and only rare cases of hypoglycemia during monotherapy were reported [42].…”

Saxagliptin and Metformin in Fixed Combination for the Treatment of Type 2 Diabetes in Adults

“…The drug has little to no plasma protein binding and saxagliptin is metabolized by CYP3A4/5 to its metabolite, which is also a DPP-4 inhibitor. Although less potent, the metabolite of saxagliptin is more selective than the parent compound 22,23. Saxagliptin is also a P-glycoprotein substrate but does not significantly inhibit or induce P-glycoprotein 21.…”

“…Saxagliptin is a selective, reversible, and competitive DPP-4 inhibitor 22,23. The incretin hormones, GIP and GLP-1, are released in a glucose-dependent manner in response to a meal 22–24.…”

“…DPP-4 rapidly inactivates the incretin hormones, decreasing their duration of action. It is present within the endothelium of various organs and has enzymatic activity in circulating plasma 3,22,23. Inhibition of DPP-4 is an attractive therapeutic mechanism which results in increased plasma concentrations of endogenous GLP-1 3.…”

Potential of pharmacological modulation of level and activity incretins on diabetes mellitus type 2

“…В 24-недельных клинических исследованиях монотерапия саксаглиптином снижала уровень гликилированного гемоглобина от 0,4% до 0,9%. Препарат не оказывал влияние на массу тела пациентов, не вызывал побочных эффектов в дозах от 2,5 до 40 мг и фиксировали лишь редкие случае гипогликемии при монотерапии [42].…”