title: Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
abstract: OBJECTIVE
  To test the effectiveness and safety of saxagliptin 5 mg/d in patients with type 2 diabetes mellitus (T2DM) with and without history of cardiovascular disease (CVD) or cardiovascular (CV) risk factors.
  
  
  METHODS
  The authors conducted a post hoc analysis of data from 3 randomized studies that compared saxagliptin versus placebo as initial combination therapy with metformin for 24 weeks (N = 648) and versus placebo as an add-on to insulin with and without metformin for 24 weeks (N = 455), and assessed noninferiority to glipizide as an add-on to metformin for 52 weeks (N = 858). Efficacy outcomes were the adjusted mean change from baseline in glycated hemoglobin (HbA1c) level, fasting plasma glucose concentration, and body weight and the proportion of patients achieving an HbA1c level < 7%. Pairwise comparisons were performed in subgroups with 1) history/no history of CVD, 2) ≥ 2 versus 0 to 1 CV risk factors, 3) hypertension/no hypertension, and 4) statin use/no statin use. Adverse events (AE) and hypoglycemia were monitored.
  
  
  RESULTS
  In the initial combination therapy study, reductions in HbA1c level from baseline were greater with saxagliptin versus placebo in all subgroups (difference [saxagliptin - placebo], -0.38% to -0.67%). In the add-on to insulin ± metformin study, differences in adjusted mean change in HbA1c level versus placebo ranged from -0.23% to -0.58% across subgroups. In the noninferiority to glipizide study, adjusted mean changes in HbA1c level were comparable between saxagliptin and glipizide, across subgroups (difference, 0.08%-0.21%). No evidence suggested clinically relevant treatment-by-subgroup interactions in pairwise comparison. Incidences of ≥ 1 AE were comparable across subgroups. Incidences of confirmed hypoglycemia with saxagliptin were 0 in both metformin add-on studies and 1.2% to 7.8% with saxagliptin + insulin ± metformin.
  
  
  CONCLUSIONS
  In patients with T2DM, saxagliptin 5 mg/d was similarly effective in improving glycemic control, with an AE profile similar to that of placebo, irrespective of CVD history, number of CV risk factors, hypertension, or statin use.
  
  
  BACKGROUND
  www.ClinicalTrials.gov identifiers: NCT00327015, NCT00575588, NCT00757588.
authors.affiliation: AstraZeneca, Wilmington, DE. william.cook@astrazeneca.com.
authors.forename: William
authors.initials: W
authors.lastname: Cook
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Minervini
authors.forename: Brian
authors.initials: B
authors.lastname: Bryzinski
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004151:Dipeptides / Q000009:adverse effects / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005215:Fasting; D005913:Glipizide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005913:Glipizide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; C502994:saxagliptin