Exenatide: effect of injection time on postprandial glucose in patients with Type 2 diabetes.
OBJECTIVE
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.
Eli Lilly and Company Limited, Lilly Research Centre, Erl Wood Manor, UK. linnebjerg_helle@lilly.com
H
H
Linnebjerg
P A
PA
Kothare
Z
Z
Skrivanek
A
A
de la Peña
M
M
Atkins
C S
CS
Ernest
M E
ME
Trautmann
D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019518:Postprandial Period; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000077270:Exenatide