EFFECT OF A NOVEL BETA-ADRENOCEPTOR AGONIST (RO-40-2148) ON RESTING ENERGY-EXPENDITURE IN OBESE WOMEN

The aim of this single-blind, placebo-controlled study was to investig ate the effects of the new beta-adrenergic compound Ro 40-2148 on rest ing energy expenditure (REE) at rest and after an oral glucose load in non-diabetic obese women before and after two weeks of treatment. Aft er one week of placebo administration and after an overnight fast and one hour rest, REE and glucose and lipid oxidation rates were measured by indirect calorimetry (hood system) before and for 6 h after a sing le dose of placebo solution. A 75 g oral glucose tolerance test (OGTT) was performed during this period starting 90 min after the placebo ad ministration. During the following two weeks, using a randomization de sign, six patients received Ro 40-2148 at a dose of 400 mg diluted in 100 ml water twice a day (i.e. 800 mg per day), while six others conti nued with the placebo administration. The same tests and measurements were repeated after two weeks, except for the treatment group which re ceived the drug instead of the placebo. The 14-day period of drug admi nistration did not increase REE measured in post-absorptive conditions . Similarly, there was no acute effect on REE of a 400 mg dose of Ro 4 0-2148. In contrast, glucose-induced thermogenesis was significantly i ncreased after two weeks in the treatment group (means +/- s.e.m.; 3.7 +/- 1.3%, P = 0.047), while no change was observed in the placebo gro up (-0.8 +/- 0.7%, not significant). Since there was no significant ch ange in the respiratory quotient, the increase in energy expenditure o bserved in the treatment group was due to stimulation of both lipid an d glucose oxidation. The drug induced no variations in heart rate, blo od pressure, axillary temperature or in plasma glucose, insulin and fr ee fatty acid levels. In conclusion, this study shows that Ro 40-2148 activates glucose-induced thermogenesis in obese non-diabetic patients .