title: Efficacy and safety of saxagliptin combination therapy in US patients with type 2 diabetes.
abstract: BACKGROUND
  The mechanism of action of dipeptidyl peptidase-4 inhibitors, such as saxagliptin, makes them suitable for combination therapy in type 2 diabetes mellitus (T2DM). Genetic, cultural, and environmental differences in individuals from different regions of the world may result in differences in treatment response to oral antidiabetic drugs (OADs). This post-hoc subanalysis assessed the efficacy and safety of saxagliptin as add-on therapy to metformin, glyburide, or a thiazolidinedione in patients with inadequately controlled T2DM in the United States.
  
  
  METHODS
  In 3 phase 3 studies of patients with T2DM uncontrolled on monotherapy, 547 adult US patients were randomized to receive saxagliptin (2.5 or 5 mg/d) or placebo as add-on to metformin, glyburide, or a thiazolidinedione (pioglitazone or rosiglitazone). Efficacy was assessed as the change from baseline to week 24 in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial glucose area under the curve (PPG-AUC) and the proportion of patients achieving HbA1c<7.0%. Pooled safety and tolerability data across trials were also analyzed.
  
  
  RESULTS
  Reductions from baseline to week 24 in HbA1c were observed in all saxagliptin treatment groups versus placebo: saxagliptin 2.5 or 5 mg plus metformin (mean difference from placebo, -0.87% and -0.89%, respectively), glyburide (-0.51% and -0.52%), or thiazolidinedione (-0.45% and -0.60%). Improvement was also observed in FPG and PPG-AUC. Adverse events for the US cohort were consistent with previously reported data from the 3 trials. The pooled incidence of reported hypoglycemia was 5.3% and 11.4% with saxagliptin 2.5 and 5 mg/d add-on, respectively, versus 6.8% with placebo add-on.
  
  
  CONCLUSIONS
  This post-hoc analysis in a cohort of US patients with T2DM uncontrolled on monotherapy suggests that saxagliptin 2.5 or 5 mg as add-on therapy to OADs results in improvement across key glycemic parameters compared with placebo add-on and was generally safe and well tolerated.
authors.affiliation: Global Clinical Research, Bristol-Myers Squibb, Princeton, NJ 08543, USA. chetan.karyekar@bms.com
authors.forename: Chetan
authors.initials: C
authors.lastname: Karyekar
authors.forename: Mark
authors.initials: M
authors.lastname: Donovan
authors.forename: Elsie
authors.initials: E
authors.lastname: Allen
authors.forename: Douglas
authors.initials: D
authors.lastname: Fleming
authors.forename: Shoba
authors.initials: S
authors.lastname: Ravichandran
authors.forename: Roland
authors.initials: R
authors.lastname: Chen
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; 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; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use; D014481:United States; D055815:Young Adult
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human; C502994:saxagliptin; C089946:2,4-thiazolidinedione