Evidence from rodent studies indicates that the -cell-derived neurohormone amylin exerts multiple effects on eating behavior, including reductions in meal size, intake of highly-palatable foods, and stress-induced sucrose consumption. To assess the effect of amylin agonism on human eating behavior, we conducted a randomized, blinded, placebo-controlled, multicenter study investigating the effects of the amylin analog pramlintide on body weight, 24-hour caloric intake, portion sizes, "fast-food" intake, and perceived control of eating in 88 obese subjects. After a 2-day placebo lead-in, subjects self-administered pramlintide (180 µg) or placebo by subcutaneous injection 15 minutes before meals for 6 weeks, without concomitant lifestyle modifications. Compared to placebo, pramlintide treatment elicited significant mean reductions from baseline in body weight on Day 44 (-2.1 ± 0.3% vs. +0.1 ± 0.4%, P<0.001), 24-hour caloric intake (-990 ± 94 kcal vs. -243 ± 126 kcal on Day 3, P<0.0001; -680 ± 86 kcal vs. -191 ± 161 kcal on Day 43, P<0.01), portion sizes, and caloric intake at a "fast-food challenge" (-385 ± 61 kcal vs. -109 ± 88 kcal on Day 44; P<0.05). Pramlintide treatment also improved perceived control of eating, as demonstrated by a 45% placebo-corrected reduction in binge eating scores (P<0.01). The results of this translational research study confirm in humans various preclinical effects of amylin agonism, demonstrating that pramlintide-mediated weight loss in obese subjects is accompanied by sustained reductions in 24-hour food intake, portion sizes, "fast-food" intake, and binge eating tendencies.