Formoterol, a highly β2-selective agonist, increases energy expenditure and fat utilisation in men

The sympathetic nervous system regulates energy metabolism via β-adrenoreceptors. Therapeutic exploitation of previous β2-adrenegic agonists for metabolic benefits has been hindered by cross stimulation of cardiac β1-adrenoceptor, causing tachycardia. Formoterol is a novel highly β2-selective adrenergic agonist and holds promise as a β2-agonist that could impart selective beneficial metabolic effects.

To investigate the metabolic effects of formoterol on energy and substrate metabolism.

Healthy volunteers.

(1) Dose-finding study, step-wise incremental design of weekly administration of 80, 160 and 320 μg daily of formoterol in four subjects and, (2) metabolic study, an open-label metabolic evaluation of 1-week treatment in eight men using a dose determined from (1).

Resting energy expenditure (EE), diet-induced thermogenesis (DIT) and fat oxidation (Fox) using indirect calorimetry, heart rate and plasma non-esterified fatty acid (NEFA) levels.

In the dose-finding study, all three doses increased resting EE and Fox with the 320 μg dose significantly increasing heart rate. In the metabolic study, the selected 160 μg daily dose increased resting EE by 13 ± 2% (P<0.001) and Fox by 23 ± 4% (P<0.01), but not DIT. Plasma NEFA levels rose by 16 ± 2% (P<0.01). Heart rate did not change significantly. Out of the eight subjects, six reported tremor and palpitation, two lost appetite and one suffered from insomnia.

At a dose of 160 μg per day, formoterol increases resting EE and fat utilization without inducing tachycardia. From this first metabolic evaluation in humans, we conclude that formoterol imparts beneficial metabolic changes that may be exploited for therapy of obesity.