A growing appreciation of the overlapping neuroendocrine mechanisms controlling energy balance has highlighted combination therapies as a promising strategy to combat the counter-regulatory physiological responses that ultimately render current anti-obesity treatments ineffective. Two such neuroendocrine systems include amylin and glucagon-like peptide-1 (GLP-1). Both amylin and GLP-1 act through distinct yet converging mechanisms in the brain and throughout the periphery to reduce feeding and body weight gain. However, individual pharmacotherapies for either system fail to maintain significant reductions in body weight over the long term. This project is looking at whether an amylin/GLP-1 combination therapy can produce greater food intake- and body weight-suppressive effects compared to monotherapies in both lean and diet-induced obese rats. Results indicate that chronic daily administration of this combination therapy leads to reduced energy intake and greater body weight loss over time compared to monotherapy-treated groups.