title: DURATION-2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide.
abstract: OBJECTIVE
  In the initial 26-week, double-blind, double-dummy assessment period of the DURATION-2 trial in patients with Type 2 diabetes on metformin, the once-weekly glucagon-like peptide 1 (GLP-1) receptor agonist exenatide once-weekly resulted in greater HbA(1c) improvement and weight reduction compared with maximum approved daily doses of sitagliptin or pioglitazone. This subsequent, 26-week, open-label, uncontrolled assessment period evaluated the safety and efficacy of (i) continued exenatide once-weekly treatment and (ii) switching from sitagliptin or pioglitazone to exenatide once-weekly.
  
  
  METHODS
  Randomised oral medications were discontinued and all patients received exenatide once-weekly. Of the 364 patients [original baseline HbA(1c) 8.5 ± 1.1% (70 mmol/mol), fasting plasma glucose 9.0 ± 2.5 mmol/l, weight 88 ± 20 kg) who continued into the open-label period, 319 patients (88%) completed 52 weeks.
  
  
  RESULTS
  Evaluable patients who received only exenatide once-weekly demonstrated significant 52-week improvements (least square mean ± se) in HbA(1c) (-1.6 ± 0.1%), fasting plasma glucose (-1.8 ± 0.3 mmol/l) and weight (-1.8 ± 0.5 kg). Evaluable patients who switched from sitagliptin to exenatide once-weekly demonstrated significant incremental improvements in HbA(1c) (-0.3 ± 0.1%), fasting plasma glucose (-0.7 ± 0.2 mmol/l) and weight (-1.1 ± 0.3 kg). Patients who switched from pioglitazone to exenatide once-weekly maintained HbA(1c) and fasting plasma glucose improvements (week 52: -1.6 ± 0.1%, -1.7 ± 0.3 mmol/l), with significant weight reduction (-3.0 ± 0.3 kg). Exenatide once-weekly was generally well tolerated and adverse events were predominantly mild or moderate in intensity. Nausea was the most frequent adverse event in this assessment period (intent-to-treat: exenatide once-weekly-only 5%; sitagliptin→exenatide once-weekly 11%; pioglitazone→exenatide once-weekly 10%). No major hypoglycaemia was observed.
  
  
  CONCLUSIONS
  Patients who switched to once-weekly exenatide from daily sitagliptin or pioglitazone had improved or sustained glycaemic control, with weight loss.
authors: Rockwood Clinic, 400 East Fifth Avenue, Spokane, WA 99202, USA. cwysham@rockwoodclinic.com
authors: C
authors: C
authors: Wysham
authors: R
authors: R
authors: Bergenstal
authors: J
authors: J
authors: Malloy
authors: P
authors: P
authors: Yan
authors: B
authors: B
authors: Walsh
authors: J
authors: J
authors: Malone
authors: K
authors: K
authors: Taylor
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057915:Drug Substitution; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000187:drug effects*; D006442:Glycated Hemoglobin / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D000077205:Pioglitazone; D011719:Pyrazines / Q000008:administration & dosage*; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D014688:Venoms / Q000008:administration & dosage*
chemical_list: D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010455:Peptides; D000077205:Pioglitazone; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones; D014230:Triazoles; D014688:Venoms