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Background:Entry of nutrients into the small intestine activates neuro-hormonal signals that regulate food intake through induction of satiation.Objective:To evaluate whether caloric intake can be decreased by pharmacologically accelerating gastric emptying (GE) of nutrients into the small intestine.Methods:Subjects were tested in 2 days, at baseline (day1) and after randomly receiving, in a double-blind manner, a 1 h infusion of erythromycin (3 mg Kg−1, to accelerate GE) or placebo (day 2). Ad libitum caloric intake and postprandial gastrointestinal symptoms were evaluated using a validated nutrient drink test, simultaneously measuring gastric by scintigraphy. Plasma levels of satiation factors were also measured to evaluate their role in the modification of caloric intake and postprandial symptoms. Acceleration of GE was assessed as the difference in percentage emptied between day 2 and day 1 (DGE). The effects of DGE on caloric intake and symptoms were evaluated using multiple (lineal) regression.Results:Among 30 overweight/obese subjects (24F and 6 M), 15 received erythromycin and 15 placebo. The overall median age was 36 years (IQR: 30-42) and body mass index was 30 Kg m−2 (IQR: 27-36). Subjects receiving erythromycin on day 2 presented accelerated GE as compared with placebo (P=0.0002). DGE at 15 min after initiating eating had a significant effect on prospective caloric intake (P=0.004). From the best-fitted regression model (R 2=81%, P<0.0001), a 10% increase in GE at 15 min induced on an average a 135±43.5 Kcal decrease in caloric intake. Postprandial increase in cholecystokinin (CCK) (P=0.03) and insulin (P=0.02) was associated with decreased caloric intake. Acceleration of GE at 60 min after initiating eating increased postprandial symptom scores measured 30 min after the completion of food consumption (P=0.01). Postprandial increase in CCK (P=0.002) and PP (P=0.02) was associated with postprandial symptoms.Conclusion:Meal size can be reduced in overweight/obese subjects by pharmacologically accelerating GE. This may be a reasonable target in obesity management. [ABSTRACT FROM AUTHOR]