title: Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus and cardiovascular disease history or cardiovascular risk factors: results of a pooled analysis of phase 3 clinical trials.
abstract: OBJECTIVE
  This post hoc analysis sought to assess the efficacy, safety, and tolerability of saxagliptin in patients with type 2 diabetes mellitus and cardiovascular (CV) risk factors or disease (CVD).
  
  
  METHODS
  Data from 5 randomized controlled trials were pooled to compare saxagliptin 5 mg with placebo: 2 studies of saxagliptin as monotherapy in drug-naïve patients and 1 each of saxagliptin as add-on therapy to metformin, glyburide, or a thiazolidinedione. Analysis was performed according to the following baseline/trial entry criteria: 1) history/no history of CVD; 2) ≥ 2 versus 0 to 1 CV risk factors; 3) statin use versus no statin use; and 4) hypertension versus no hypertension. Change from baseline glycated hemoglobin (HbA1c), fasting plasma glucose, and postprandial glucose levels; and the proportion of patients achieving an HbA1c level < 7% were analyzed (week 24). Safety was assessed by adverse events, hypoglycemia, and body weight.
  
  
  RESULTS
  In total, 882 patients received saxagliptin 5 mg and 799 received placebo. Differences in adjusted mean change from baseline HbA1c (95% CI) were greater with saxagliptin compared with placebo in patients with a history of CVD (-0.64% [-0.90 to -0.38]) and no history of CVD (-0.68% [-0.78 to -0.58]); with ≥ 2 CV risk factors (-0.73% [-0.85 to -0.60]) and 0 to 1 CV risk factor (-0.62% [-0.75 to -0.48]); with statin use (-0.70% [-0.89 to -0.52]) and no statin use (-0.66% [-0.77 to -0.56]); and with hypertension (-0.69% [-0.82 to -0.57]) and no hypertension (-0.66% [-0.80 to -0.52]). Saxagliptin was well tolerated, with similar adverse event rates and types compared with placebo. There was a < 1% rate of confirmed hypoglycemia in all groups except in patients with CV history who received placebo (2.1%).
  
  
  CONCLUSIONS
  Saxagliptin improved glycemic measures, resulted in low rates of confirmed hypoglycemia, and was well tolerated in patients with or without CVD and CV risk factors.
authors.affiliation: Medical Affairs, AstraZeneca, Wilmington, DE 19850, USA. william.cook@astrazeneca.com
authors.forename: William
authors.initials: W
authors.lastname: Cook
authors.forename: Brian
authors.initials: B
authors.lastname: Bryzinski
authors.forename: Jill
authors.initials: J
authors.lastname: Slater
authors.forename: Robert
authors.initials: R
authors.lastname: Frederich
authors.forename: Elsie
authors.initials: E
authors.lastname: Allen
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005905:Glyburide / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; C502994:saxagliptin; C089946:2,4-thiazolidinedione; D000218:Adamantane; D005905:Glyburide