Exenatide: effect of injection time on postprandial glucose in patients with Type 2 diabetes

Diabet Med. 2006 Mar;23(3):240-5. doi: 10.1111/j.1464-5491.2006.01800.x.


Aims: Exenatide is an incretin mimetic whose effect on glycaemic control in patients with Type 2 diabetes is currently under investigation. This study assessed the effect of injection time relative to a standardized meal on postprandial pharmacodynamics of exenatide in patients with Type 2 diabetes.

Methods: Eighteen patients participated in this single-centre, open-label, placebo-controlled, randomized, six-way crossover study. Patients received subcutaneous injections of either placebo (-15 min) or 10 microg of exenatide at -60, -15, 0, +30 or +60 min relative to a standardized breakfast meal on six consecutive days. Serial blood samples were assayed for plasma glucose and insulin concentrations.

Results: For all exenatide treatments, incremental postprandial glucose area under the postprandial plasma glucose curve from zero to 6 h (AUC0-6 h) was significantly reduced compared with placebo. When exenatide was administered before (-60, -15 min) or with the meal (0 min), peak postprandial glucose concentrations were significantly decreased (P < 0.0001 for all treatments) compared with placebo. Post-meal exenatide administration (+30, P < 0.05; +60 min, P = 0.21) resulted in smaller peak glucose reductions and in some patients transient low plasma glucose concentrations were reported. Peak plasma insulin concentrations in the pre-meal treatments were significantly lower than placebo (P < 0.05 for all treatments), while post-meal dosing groups exhibited a trend towards higher insulin peaks compared with placebo. The most common adverse events related to exenatide were headache, nausea, dyspepsia and vomiting, and were generally of mild-to-moderate intensity.

Conclusions: In this study, all exenatide treatments demonstrated reductions in postprandial plasma glucose excursions compared with placebo. Pre-meal and with meal administration of exenatide produced greater reduction of postprandial glucose excursions compared with post-meal administration. These data support flexible dosing of exenatide at any time within 60 min before a meal.

Publication types

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

MeSH terms

  • Area Under Curve
  • Blood Glucose / analysis*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Administration Schedule
  • Exenatide
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Injections, Subcutaneous
  • Insulin / blood
  • Male
  • Middle Aged
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Peptides / pharmacokinetics
  • Postprandial Period
  • Venoms / administration & dosage*
  • Venoms / adverse effects
  • Venoms / pharmacokinetics


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Peptides
  • Venoms
  • Exenatide