DURATION-2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide

Diabet Med. 2011 Jun;28(6):705-14. doi: 10.1111/j.1464-5491.2011.03301.x.

Abstract

Aims: 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.

Trial registration: ClinicalTrials.gov NCT00637273.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Substitution
  • Exenatide
  • Female
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / drug effects*
  • Glycated Hemoglobin A / drug effects*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Peptides / administration & dosage*
  • Pioglitazone
  • Pyrazines / administration & dosage*
  • Sitagliptin Phosphate
  • Thiazolidinediones / administration & dosage*
  • Treatment Outcome
  • Triazoles / administration & dosage*
  • Venoms / administration & dosage*

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Pyrazines
  • Thiazolidinediones
  • Triazoles
  • Venoms
  • Glucagon-Like Peptide 1
  • Metformin
  • Exenatide
  • Sitagliptin Phosphate
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT00637273