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

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.

• Authors: C Wysham, R Bergenstal, J Malloy, P Yan, B Walsh, J Malone, K Taylor
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 28 Issue 6 Pg. 705-14 (Jun 2011) ISSN: 1464-5491 [Electronic] England
• PMID: 21434995 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Amylin Pharmaceuticals, Inc. Diabetic Medicine © 2011 Diabetes UK.

Chemical References

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

Topics

• Diabetes Mellitus, Type 2 (blood, drug therapy, physiopathology)
• Double-Blind Method
• Drug Administration Schedule
• Drug Substitution
• Exenatide
• Female
• Glucagon-Like Peptide 1 (blood, drug effects)
• Glycated Hemoglobin (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)