Meal size can be decreased in obese subjects through pharmacological acceleration of gastric emptying (The OBERYTH trial)

Abstract

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 À1 , 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 À2 (IQR: 27-36). Subjects receiving erythromycin on day 2 presented accelerated GE as compared with placebo (P ¼ 0.0002). DGE at 15 min after initiating eating had a significant effect on prospective caloric intake (P ¼ 0.004). From the best-fitted regression model (R 2 ¼ 81%, Po0.0001), 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 ¼ 0.03) and insulin (P ¼ 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 ¼ 0.01). Postprandial increase in CCK (P ¼ 0.002) and PP (P ¼ 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.

Cyclic vomiting syndrome and functional vomiting in adults: association with cannabinoid use in males

“… 31 showed that the effects of erythromycin, which accelerate GE, were significantly associated with postprandial symptoms including nausea. Other studies 32,33 also observed that accelerated GE by a drug or its presence in patients with functional dyspepsia was associated with nausea. One limitation of the present study is that we only had GE measurements on a subset (57%), and it is possible, albeit unlikely, that the study population assessed was not representative.…”

The effects of weight loss strategies on gastric emptying and appetite control

“…Torra et al . (118) provided the first evidence supporting the hypothesis that pharmacologically accelerating gastric emptying could enhance satiation and reduce meal size. Erythromycin administration in obese individuals exerted a faster gastric emptying in the first 15 min after initiation of eating, which translated into a small reduction in energy intake (135 kcal) compared to individuals who received placebo.…”

“…However, an overall faster gastric emptying time, despite potentially enhancing the magnitude of satiety sensations from intestinal factors between meals, is likely to lead to decreased feelings of fullness arising from the stomach and shorten the interval to the onset of the next meal. Thus, meal frequency may be increased and hence net energy intake may not be reduced (118). For weight loss, the most effective strategy to reduce energy intake will be one that targets satiation, satiety and snacking behaviour by manipulating the emptying rate to maximize both the sensation of fullness from the stomach, and the early onset and prolonged release of gut peptides from the intestine.…”

“…In contrast, findings of slowed gastric emptying with the cannabinoid dronabinol led to speculation that faster gastric emptying and enhanced satiation may be one mechanism behind the appetite and weight reducing effects of Rimonabant, a cannabinoid antagonist (117). Torra et al (118) provided the first evidence supporting the hypothesis that pharmacologically accelerating gastric emptying could enhance satiation and reduce meal size. Erythromycin administration in obese individuals exerted a faster gastric emptying in the first 15 min after initiation of eating, which translated into a small reduction in energy intake (135 kcal) compared to individuals who received placebo.…”

Gastrointestinal Physiological Changes and Their Relationship to Weight Loss Following the POSE Procedure

“…Caloric intake measured by the nutrient drink test has been shown to correlate well with caloric intake during a buffet meal [15,16]. It has shown good reproducibility and sensitivity to change and has been tested in health, normal weight, and obese populations [17,18].…”