Effects on metabolic rate and fuel selection of a selective beta-3 agonist (ICI D7114) in healthy lean men

ICI D7114 is a selective beta-3 agonist which in some animals increases metabolic rate, promotes weight loss and improves glucose tolerance. To investigate its potential usefulness in humans, 16 healthy young men (mean age 28.9 +/- 8.0 years; body mass index 22.5 +/- 1.6 kg/m2) were given ICI D7114 (150 mg/day, 2.08 +/- 0.24 mg/kg body weight) or placebo for 14 days in a double-blind randomised parallel group trial. Energy expenditure (EE) and substrate oxidation were assessed by continuous whole-body indirect calorimetry on Day 0 (before dosing), on day 1 (acute effect) and on Day 14 (chronic effect).

Analysis of covariance indicated no significant effects on EE 4 h post-dose (Day 1, +2.4%, NS; Day 14, +1.0%, NS). There was no chronic effect on either the lowest 1 h of sleeping EE (+2.2%, NS) or 24 h EE (+0.7%, NS). There was a marginally significant chronic stimulation of basal metabolic rate (+3.6%, P = 0.042). ICI D7114 had no significant influence on protein, fat or carbohydrate oxidation. Tolerability and safety data showed that there were no increases in resting heart rate or blood pressure; no change in plasma potassium or reports of tremor; no haematological or biochemical abnormalities and no adverse events.

We conclude that over 14 days ICI D7114 at a dose level of 150 mg/day has no biologically significant effect on EE in healthy, lean men.