Smith, Steven R., Blundell, John E., Burns, Colleen, Ellero, Cinzia, Schroeder, Brock E., Kesty, Nicole C., Chen, Kim S., Halseth, Amy E., Lush, Cameron W., and Weyer, Christian
Evidence from rodent studies indicates that the [beta]-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-h 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 [micro]g) or placebo by subcutaneous injection 15 rain before meals for 6 wk without concomitant lifestyle modifications. Compared with placebo, pramlintide treatment elicited significant mean reductions from baseline in body weight on day 44 (-2.1 [+ or-] 0.3 vs. +0.1 [+ or-] 0.4%, P < 0.001), 24-h caloric intake (-990 [+ or-] 94 vs. -243 [+ or-] 126 kcal on day 3, P < 0.0001; -680 [+ or-] 86 vs. -191 [+ or-] 161 kcal on day 43, P < 0.01), portion sizes, and caloric intake at a 'fast food challenge' (-385 [+ or-] 61 vs. -109 [+ or-] 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-h food intake, portion sizes, fast food intake, and binge eating tendencies. obesity; weight loss; satiety; food intake; neuroendocrine hormones more...