The present disclosure provides binding agents that modulate the interaction between LEAP2 and GHSR. Specifically, the present disclosure provides binding agents, such as LEAP2 peptides that bind GHSR and methods of their use to treat, ameliorate, or prevent a neuroendocrine and/or metabolic disease or disorder such as obesity, diabetes, acromegaly, gigantism and/or Prader-Willi syndrome. The present disclosure also provides binding agents, such as antibodies, that bind LEAP2, and methods of their use, to treat, ameliorate, or prevent a neuroendocrine and/or metabolic disease or disorder such as cachexia, anorexia, or other wasting syndromes.