Amylin Analogue in the Treatment of Obesity

Kim, Chul Sik

Abstract

Obesity is now the major contributor to cardiovascular disease, diabetes mellitus, sleep apnea, musculoskeletal disorders and certain cancers, as well as many psychosocial disorders. The primary management of obesity is dieting and physical exercise. To supplement this, or in case of failure, anti-obesity drugs may be taken to reduce appetite or inhibit fat absorption. However, current pharmacological interventions have displayed limited efficacy and unpleasant side-effects. The lines of communication between the gastrointestinal tract and central nervous system form a key component in a recently established model of appetite regulation. Currently, amylin receptor agonist is emerging as part of an integrated neurohormonal therapeutic approach for managing diabetes mellitus and body weight. Amylin is a 37 amino acid peptide that is co-released with insulin from pancreatic beta-cells. Stimuli for release and post-prandial profiles closely imitate those of insulin. Obese subjects with a normal glucose profile actually exhibit fasting hyperamylinemia. Post-prandially diabetic and non-diabetic obese subjects show increased amylin levels. However, the human studies show no evidence of amylin resistance in obese individuals or at least exogenous amylin administration appears to overcome any resistance at target tissues. Pramlintide is a non-amyloidogenic analogue of amylin. This medicine is already licensed in the United States as an adjunct to insulin therapy in both type 1 and type 2 diabetes. In addition to a modest glucose lowering effects and a reduction in insulin requirements, pramlintide has also shown reductions in body weight. Therefore some researchers are currently investigating whether pramlintide could be an effective weight-loss agent.