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.