Published in:
01-01-2010 | Short Communication
Effects of exenatide on circulating glucose, insulin, glucagon, cortisol and catecholamines in healthy volunteers during exercise
Published in: Diabetologia | Issue 1/2010
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Aims/hypothesis
Exenatide, a glucagon like peptide-1 agonist, is a treatment for type 2 diabetes mellitus that stimulates insulin and suppresses glucagon secretion in a glucose-dependent manner. By contrast, during aerobic exercise, the serum insulin concentration normally falls, with a rise in plasma glucagon. We therefore assessed whether exenatide might predispose to hypoglycaemia during exercise.
Methods
We studied eight non-diabetic men, who were 35.3 ± 6.3 years of age with BMI of 24.7 ± 1.7 kg/m2 (mean ± SD), using a randomised, crossover, double-blind design investigation. After an overnight fast, participants received 5 μg of subcutaneous exenatide or placebo and rested for 105 min before cycling at 60% of their maximal oxygen uptake (\( \dot V{{\text{O}}_{\text{2max}}} \)) for 75 min and then recovering for a further 60 min.
Results
The insulin/glucagon molar ratio rose with exenatide at rest (p < 0.01), then fell during exercise with placebo and with exenatide. At rest, fasting blood glucose fell by approximately 1 mmol/l with exenatide to a nadir of 3.4 ± 0.1 mmol/l (p < 0.01). During exercise, blood glucose fell with placebo but, unexpectedly, rose with exenatide. Plasma adrenaline (epinephrine) and noradrenaline (norepinephrine), but not cortisol concentrations increased to a greater extent during exercise after exenatide. No participant developed symptomatic hypoglycaemia and the lowest individual blood glucose recorded was 2.8 mmol/l with exenatide at 50 min in the pre-exercise period.
Conclusions/interpretation
In non-diabetic participants given exenatide, blood glucose concentrations rise rather than fall during aerobic exercise with an associated greater catecholamine response.