DURATION-5: Exenatide Once Weekly Resulted in Greater Improvements in Glycemic Control Compared With Exenatide Twice Daily in Patients With Type 2 Diabetes

J Clin Endocrinol Metab. 2011 May;96(5):1301-10. doi: 10.1210/jc.2010-2081. Epub 2011 Feb 9.

Abstract

Context: We wanted to understand the effects of once-weekly vs. twice-daily glucagon-like peptide-1 receptor agonism for treatment of patients with type 2 diabetes.

Objective: The objective of the study was to compare effects of exenatide once weekly (ExQW) and exenatide twice daily (ExBID) on glycemic control, body weight, and safety.

Design: This was a 24-wk, randomized, open-label, comparator-controlled study.

Setting: The study was conducted at 43 sites in the United States.

Patients: The study population was 252 intent-to-treat patients with type 2 diabetes [baseline (mean ± SD): glycosylated hemoglobin (HbA1c) 8.4 ± 1.2%, fasting plasma glucose 171 ± 47 mg/dl, weight 96 ± 20 kg] that were drug naïve (19%) or previously treated with one (47%) or multiple (35%) oral antidiabetic medications.

Interventions: Interventions included ExQW 2 mg for 24 wk or ExBID 5 μg for 4 wk followed by ExBID 10 μg for 20 wk.

Main outcome measure: The change in HbA1c from baseline to wk 24 was measured.

Results: At 24 wk, ExQW produced significantly greater changes from baseline (least squares mean ± SE) vs. ExBID in HbA1c (-1.6 ± 0.1% vs. -0.9 ± 0.1%; P < 0.0001) and fasting plasma glucose (-35 ± 5 mg/dl vs. -12 ± 5 mg/dl; P = 0.0008). Similar reductions in mean body weight from baseline to wk 24 were observed in both groups (-2.3 ± 0.4 kg and -1.4 ± 0.4 kg). Both treatments were generally well tolerated. Transient and predominantly mild to moderate nausea, the most frequent adverse event, was less common with ExQW (14%) than with ExBID (35%). Injection-site reactions were infrequent, but more common with ExQW. No major hypoglycemia occurred.

Conclusions: Continuous glucagon-like peptide-1 receptor agonism with ExQW resulted in superior glycemic control, with less nausea, compared with ExBID in patients with type 2 diabetes. Both groups lost weight.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / metabolism*
  • Blood Pressure / physiology
  • Body Weight / physiology
  • Chromatography, High Pressure Liquid
  • Combined Modality Therapy
  • Delayed-Action Preparations
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Exenatide
  • Exercise Therapy
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Peptides / therapeutic use*
  • Risk Factors
  • Venoms / administration & dosage*
  • Venoms / adverse effects
  • Venoms / therapeutic use*
  • Weight Loss / drug effects
  • Young Adult

Substances

  • Blood Glucose
  • Delayed-Action Preparations
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Exenatide