title: Utility of Saxagliptin in the Treatment of Type 2 Diabetes: Review of Efficacy and Safety.
abstract: BACKGROUND
  Type 2 diabetes mellitus (T2DM) is a complex disease in which multiple organs and hormones contribute to the pathogenesis of disease. The intestinal hormone, glucagon-like peptide-1 (GLP-1), secreted in response to nutrient ingestion, increases insulin secretion from pancreatic β-cells and reduces glucagon secretion from pancreatic α-cells. GLP-1 is inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme. Saxagliptin is a DPP-4 inhibitor that prevents the degradation of endogenous GLP-1 and prolongs its actions on insulin and glucagon secretion. This article reviews the efficacy and safety of saxagliptin in patients with T2DM.
  
  
  METHODS
  A PubMed literature search was conducted to identify relevant, peer-reviewed saxagliptin clinical trial articles published between January 2008 and June 2015. Search terms included "saxagliptin" and "DPP-4 inhibitors".
  
  
  RESULTS
  In clinical trials, saxagliptin significantly improved glycemic control when used as monotherapy or as add-on therapy to other antidiabetes agents and was associated with a low risk of hypoglycemia. In a large cardiovascular (CV) outcomes trial (SAVOR) in patients with T2DM and with established CV disease or multiple CV risk factors, saxagliptin neither increased nor decreased CV risk compared with placebo as assessed by the composite end point of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke. Unexpectedly, more patients in the saxagliptin (3.5%) than in the placebo group (2.8%) were hospitalized for heart failure.
  
  
  CONCLUSIONS
  Saxagliptin demonstrated statistically significant and clinically meaningful improvements in glycemic control and a low risk of hypoglycemia in patients with T2DM. However, this positive profile needs to be tempered by the observation of an increased risk of hospitalization for heart failure in the SAVOR trial. Results from ongoing CV outcome trials with other DPP-4 inhibitors may provide additional data on how best to manage patients with T2DM who are at risk for heart failure.
  
  
  BACKGROUND
  AstraZeneca LP.
authors.affiliation: Aurora Advanced Healthcare, Milwaukee, WI, USA. Rajeev.Jain@aurora.org.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Jain
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D004151:Dipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1; C502994:saxagliptin; D000218:Adamantane
keywords: Antidiabetes drugs; Dipeptidyl peptidase-4 inhibitor; Saxagliptin; Type 2 diabetes mellitus