title: Saxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial.
abstract: OBJECTIVE
  To assess the efficacy and safety of saxagliptin vs. glipizide as add-on therapy to metformin in patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin alone.
  
  
  METHODS
  A total of 858 patients [age ≥ 18 years; glycated haemoglobin (HbA(1c) ) > 6.5 - 10.0%; on stable metformin doses ≥ 1500 mg/day] were randomised 1 : 1 to saxagliptin 5 mg/day or glipizide up-titrated as needed from 5 to 20 mg/day for 52 weeks. The primary objective was to assess if the change from baseline HbA(1c) achieved with saxagliptin plus metformin was non-inferior to glipizide plus metformin.
  
  
  RESULTS
  The per-protocol analysis demonstrated non-inferiority of saxagliptin vs. glipizide; adjusted mean changes from baseline HbA(1c) were -0.74% vs. -0.80%, respectively; the between-group difference was 0.06% (95% CI, -0.05% to 0.16%). Treatment with saxagliptin vs. glipizide was associated with a significantly smaller proportion of patients with hypoglycaemic events (3.0% vs. 36.3%; p < 0.0001) and a divergent impact on body weight (adjusted mean change from baseline -1.1 kg with saxagliptin vs. 1.1 kg with glipizide; p < 0.0001). There was a significantly smaller rise in HbA(1c) (%/week) from week 24 to 52 with saxagliptin vs. glipizide (0.001% vs. 0.004%; p = 0.04) indicating a sustained glycaemic effect beyond week 24. Excluding hypoglycaemic events, the proportion of patients experiencing adverse events (AEs) was similar (60.0% saxagliptin vs. 56.7% glipizide); treatment-related AEs were less common with saxagliptin vs. glipizide (9.8% vs. 31.2%), attributable to the higher frequency of hypoglycaemia in glipizide patients. Discontinuation rates resulting from AEs were similar (∼4%).
  
  
  CONCLUSIONS
  Saxagliptin plus metformin was well tolerated, provided a sustained HbA(1c) reduction over 52 weeks, and was non-inferior to glipizide plus metformin, with reduced body weight and a significantly lower risk of hypoglycaemia.
authors.affiliation: Hospital of the Ludwig Maximilian, University of Munich, Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Göke
authors.forename: B
authors.initials: B
authors.lastname: Gallwitz
authors.forename: J
authors.initials: J
authors.lastname: Eriksson
authors.forename: A
authors.initials: A
authors.lastname: Hellqvist
authors.forename: I
authors.initials: I
authors.lastname: Gause-Nilsson
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005913:Glipizide / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005913:Glipizide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; C502994:saxagliptin