title: A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of saxagliptin as add-on therapy in adults with type 2 diabetes with inadequate glycaemic control on metformin plus a sulphonylurea.
  
  
  METHODS
  In this 24-week, multicentre, randomized, parallel-group, double-blind study, outpatients aged ≥18 years with type 2 diabetes, body mass index ≤40 kg/m(2) and inadequate glycaemic control, received saxagliptin 5 mg or placebo once-daily added to background medication consisting of a stable maximum tolerated dose of metformin plus a sulphonylurea. The primary end point was change in glycated haemoglobin (HbA1c) from baseline to week 24. Safety and tolerability assessments included adverse events (AEs), hypoglycaemia and body weight.
  
  
  RESULTS
  A total of 257 patients were randomized, treated and included in the safety analysis (saxagliptin, n = 129; placebo, n = 128); 255 were included in the efficacy analysis (saxagliptin, n = 127; placebo, n = 128). HbA1c reduction was greater with saxagliptin versus placebo [between-group difference in adjusted mean change from baseline, -0.66%; 95% confidence interval (CI), -0.86 to -0.47 (7 mmol/mol, -9.4 to -5.1); p < 0.0001]. The proportion of patients with ≥1 AE was 62.8% with saxagliptin and 71.7% with placebo. In the saxagliptin and placebo groups, rates of reported hypoglycaemia were 10.1 and 6.3%, respectively, and rates of confirmed hypoglycaemia (symptoms + glucose < 2.8 mmol/l) were 1.6 and 0%. Mean change in body weight was 0.2 kg for saxagliptin and -0.6 kg for placebo (p = 0.0272).
  
  
  CONCLUSIONS
  Addition of saxagliptin 5 mg/day in patients inadequately controlled on metformin and sulphonylurea effectively improved glycaemic control and was well tolerated.
authors.affiliation: Wollongong Diabetes Service, Illawarra Shoalhaven Local Health District, Wollongong, Australia.
authors.forename: R G
authors.initials: RG
authors.lastname: Moses
authors.forename: S
authors.initials: S
authors.lastname: Kalra
authors.forename: D
authors.initials: D
authors.lastname: Brook
authors.forename: J
authors.initials: J
authors.lastname: Sockler
authors.forename: J
authors.initials: J
authors.lastname: Monyak
authors.forename: J
authors.initials: J
authors.lastname: Visvanathan
authors.forename: M
authors.initials: M
authors.lastname: Montanaro
authors.forename: S A
authors.initials: SA
authors.lastname: Fisher
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D001315:Australia / Q000453:epidemiology; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D002170:Canada / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007194:India / Q000453:epidemiology; D007723:Korea / Q000453:epidemiology; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D013785:Thailand / Q000453:epidemiology; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C502994:saxagliptin
keywords: DPP-4 inhibitor; antidiabetic drug; clinical trial; glycaemic control; incretin therapy; type 2 diabetes