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

Abstract

Evidence from rodent studies indicates that the β-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.

Amylin Receptor Signaling in the Ventral Tegmental Area is Physiologically Relevant for the Control of Food Intake

“…Given that amylin can penetrate the blood-brain barrier (Banks et al, 1995), gaining direct access to distributed CNS nuclei controlling for energy balance, this raises the intriguing possibility that the VTA may also be a clinically relevant site mediating the food intake-and BW-suppressive effects of systemically administered amylin analogs. Indeed, amylin analogs are already used clinically to treat diabetes mellitus (Singh-Franco et al, 2007) and have the additional effects of reducing food intake, BW, and appetite in humans (Chapman et al, 2007;Smith et al, 2007). Current results should therefore broaden the understanding of the behavioral and neuronal mechanisms that mediate the aforementioned clinical findings and also promote future imaging research examining neural activation in the mesolimbic reward system (specifically the VTA) of humans receiving amylin analogs for diabetes/obesity treatment.…”

“…Because of its potent ability to improve glycemic control (Scherbaum, 1998), the amylin analog pramlintide is FDA approved for the treatment of both type 1 and type 2 diabetes mellitus (Singh-Franco et al, 2007). In addition, amylin and amylin receptor agonists such as pramlintide and salmon calcitonin (sCT) reduce food intake and body weight (BW) when administered peripherally or into the cerebroventricular system (Chapman et al, 2007;Lutz et al, 2000;Reidelberger et al, 2002;Roth et al, 2006;Rushing et al, 2000;Smith et al, 2007), making amylinbased pharmacotherapies attractive as potential obesity treatments.…”

Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

“…Pramlintide, a synthetic analog of human amylin, has been shown in obese subjects to reduce single meal and 24-h food intake. 10,11 With longer term administration, pramlintide treatment induced placebo-corrected weight loss of 3.7% over 16 weeks, and up to 6.8% at 1 year. 10 The most common adverse event in these trials was nausea, which was primarily mild to moderate and transient in nature.…”

Effects of single or combined administration of salmon calcitonin and omega-3 fatty acids vs. diclofenac sodium in sodium monoiodoacetate-induced knee osteoarthritis in male Wistar rats

“…Even though several animal models have been used for studying the pathogenesis of OA [5], the initiation of this disease by intra-articular injection of sodium monoiodoacetate (MIA) is one of the most widely used methods [6]. MIA triggers a pro-inflammatory response, and attenuates the glyceraldehye-3-phosphate dehydrogenase activity in chondrocytes, resulting in the alteration of glycolytic process and cell death [7].…”