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TRANSLATIONAL PHYSIOLOGY

Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6-wk translational research study

¹Pennington Biomedical Research Center, Baton Rouge, Louisiana; ²University of Leeds, Leeds, United Kingdom; and ³Amylin Pharmaceuticals Incorporated, San Diego, California

Submitted 6 April 2007 ; accepted in final form 11 May 2007

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-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 µg) or placebo by subcutaneous injection 15 min 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 ± 0.3 vs. +0.1 ± 0.4%, P < 0.001), 24-h caloric intake (–990 ± 94 vs. –243 ± 126 kcal on day 3, P < 0.0001; –680 ± 86 vs. –191 ± 161 kcal on day 43, P < 0.01), portion sizes, and caloric intake at a "fast food challenge" (–385 ± 61 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-h food intake, portion sizes, fast food intake, and binge eating tendencies.

obesity; weight loss; satiety; food intake; neuroendocrine hormones

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