Chronic pramlintide decreases feeding via a reduction in meal size in male rats

Amylin, a pancreatic hormone, is well-established to suppress feeding by enhancing satiation. Pramlintide, an amylin analog that is FDA-approved for the treatment of diabetes, has also been shown to produce hypophagia. However, the behavioral mechanisms underlying the ability of pramlintide to suppress feeding are unresolved. We hypothesized that systemic pramlintide administration in rats would reduce energy intake, specifically by reducing meal size. Male rats were given b.i.d. administration of intraperitoneal pramlintide or vehicle for 1 week, and chow intake, meal patterns, and body weight were monitored throughout the test period. Consistent with our hypothesis, pramlintide decreased chow intake mainly via suppression of meal size, with corresponding reductions in meal duration on several days. Fewer effects on meal number or feeding rate were detected. Pramlintide also reduced weight gain over the 1-week study. These results highlight that the behavioral mechanisms by which pramlintide produces hypophagia are similar to those driven by amylin itself, and provide important insight into the ability of this pharmacotherapy to promote negative energy balance over a period of chronic administration.