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

Am J Health Syst Pharm. 2010 Sep 15;67(18):1515-25. doi: 10.2146/ajhp090555.

Abstract

Purpose: The pharmacology, pharmacokinetics, efficacy, safety, and dosage and administration of saxagliptin are reviewed.

Summary: Saxagliptin is a selective, reversible inhibitor of dipeptidyl peptidase-4 (DPP-4) approved for the treatment of type 2 diabetes mellitus in adults. By inhibiting DPP-4, saxagliptin reduces the degradation of endogenous incretin hormones, resulting in increased glucose-dependent insulin release and decreased glucagon secretion from the pancreas. Saxagliptin is rapidly absorbed after oral administration, and its pharmacokinetic profile allows for once-daily oral administration. Clinical trials of saxagliptin as monotherapy and as combination therapy with other oral antidiabetic medications including metformin, glyburide, pioglitazone, and rosiglitazone have demonstrated clinical benefits in various glycemic endpoints, including glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), and postprandial glucose (PPG) levels over 24 to 102 weeks of therapy. Due to its glucose-dependent mechanism of action, saxagliptin as monotherapy or in combination with metformin results in a low risk for hypoglycemia in patients with type 2 diabetes. Saxagliptin was generally well tolerated in clinical trials, with headache, upper-respiratory-tract infection, and urinary tract infection being the most common adverse events. Saxagliptin has demonstrated a low risk for drug-drug interactions. For patients with moderate or severe renal impairment or end-stage renal disease or patients taking a strong inhibitor of cytochrome P-450 isoenzyme 3A4 or 3A5, the recommended dosage is 2.5 mg once daily.

Conclusion: Saxagliptin, a DPP-4 inhibitor approved for the treatment of type 2 diabetes, demonstrated safety and efficacy in lowering HbA(1c), FPG, and PPG levels as both monotherapy and in combination with other oral antidiabetic medications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology
  • Adamantane / therapeutic use
  • Adult
  • Animals
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dipeptides / adverse effects
  • Dipeptides / pharmacology
  • Dipeptides / therapeutic use*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Incretins / metabolism

Substances

  • Blood Glucose
  • Dipeptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Incretins
  • saxagliptin
  • Adamantane