ABSTRACT
OBJECTIVE: We previously reported that a single preprandial injection (120 microg) of pramlintide, an analog of the beta-cell hormone amylin, reduced ad libitum food intake in obese subjects. To further characterize the meal-related effects of amylin signaling in humans, we studied a lower pramlintide dose (30 microg) in normal-weight subjects. RESEARCH METHODS AND PROCEDURES: In a randomized, double-blind, placebo-controlled, cross-over study, 15 healthy men (age, 24 +/- 7 years; BMI, 22.2 +/- 1.8 kg/m(2)) underwent a standardized buffet meal test on two occasions. After an overnight fast, subjects received a single subcutaneous injection of pramlintide (30 microg) or placebo, followed immediately by a standardized pre-load meal. After 1 hour, subjects were offered an ad libitum buffet meal, and total caloric intake and meal duration were measured. RESULTS: Compared with placebo, pramlintide reduced total caloric intake (1411 +/- 94 vs. 1190 +/- 117 kcal; Delta, -221 +/- 101 kcal; -14 +/- 9%; p = 0.05) and meal duration (36 +/- 2 vs. 31 +/- 3 minutes; Delta, -5.1 +/- 1.4 minutes; p < 0.005). Visual analog scale profiles of hunger trended lower and fullness higher during the first hour after pramlintide administration. In response to the buffet, hunger and fullness changed to a similar degree after pramlintide and placebo, despite subjects on pramlintide consuming 14% fewer kilocalories. Visual analog scale nausea ratings remained near baseline, without differences between treatments. Plasma peptide YY, cholecystokinin, and ghrelin concentrations did not differ with treatment, whereas glucagon-like peptide-1 concentrations after meals were lower in response to pramlintide than to placebo. DISCUSSION: These observations add support to the concept that amylin agonism may have a role in human appetite control.
