title: Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin, sulphonylurea, or thiazolidinedione). This 18-week, phase 3b, multicentre, double-blind, noninferiority trial compared the efficacy and safety of two dipeptidyl peptidase-4 inhibitors, saxagliptin and sitagliptin, in patients whose glycaemia was inadequately controlled with metformin.
  
  
  METHODS
  Adult type 2 diabetes mellitus patients (N = 801) with glycated haemoglobin (HbA(1c)) 6.5-10% on stable metformin doses (1500-3000 mg/day) were randomized 1 : 1 to add-on 5 mg saxagliptin or 100 mg sitagliptin once daily for 18 weeks. The primary efficacy analysis was a comparison of the change from baseline HbA(1c) at week 18 in per-protocol patients. Noninferiority was concluded if the upper limit of the two-sided 95% confidence interval of the HbA(1c) difference between treatments was < 0.3%.
  
  
  RESULTS
  The adjusted mean changes in HbA(1c) following the addition of saxagliptin or sitagliptin to stable metformin therapy were - 0.52 and - 0.62%, respectively. The between-group difference was 0.09% (95% confidence interval, - 0.01 to 0.20%), demonstrating noninferiority. Both treatments were generally well tolerated; incidence and types of adverse events were comparable between groups. Hypoglycaemic events, mostly mild, were reported in approximately 3% of patients in each treatment group. Body weight declined by a mean of 0.4 kg in both groups.
  
  
  CONCLUSIONS
  Saxagliptin added to metformin therapy was effective in improving glycaemic control in patients with type 2 diabetes mellitus inadequately controlled by metformin alone; saxagliptin plus metformin was noninferior to sitagliptin plus metformin, and was generally well tolerated.
authors.affiliation: University of Liège, Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit, CHU Liège, Liège, Belgium. Andre.Scheen@chu.ulg.ac.be
authors.forename: André J
authors.initials: AJ
authors.lastname: Scheen
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charpentier
authors.forename: Carl Johan
authors.initials: CJ
authors.lastname: Ostgren
authors.forename: Asa
authors.initials: A
authors.lastname: Hellqvist
authors.forename: Ingrid
authors.initials: I
authors.lastname: Gause-Nilsson
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / 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; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C517652:hemoglobin A1c protein, human; C502994:saxagliptin