1. ^*Department of Medicine, University of Adelaide, Royal Adelaide Hospital, North Terrace, Adelaide, Australia;
2. ^†Amylin Pharmaceuticals, Inc., San Diego, California.

Correspondence: Christian Weyer Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, San Diego, CA 92121. E-mail: cweyer@amylin.com

^*The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 4 November 2005; Revised  0000; Accepted 17 November 2006.

Abstract

Objective: We previously reported that a single preprandial injection (120 g) of pramlintide, an analog of the -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 g) 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/m²) underwent a standardized buffet meal test on two occasions. After an overnight fast, subjects received a single subcutaneous injection of pramlintide (30 g) 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; , -221 101 kcal; -14 9%; p = 0.05) and meal duration (36 2 vs. 31 3 minutes; , -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.