The present disclosure provides binding agents that modulate the interaction between liver-expressed antimicrobial peptide 2 (LEAP2) and growth hormone secretagogue receptor (GHSR). Specifically, the present disclosure provides binding agents, such as LEAP2 peptides that bind GHSR and methods of their use to treat or ameliorate 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, e.g., treat or ameliorate a neuroendocrine and/or metabolic disease or disorder such as cachexia, anorexia, or other wasting syndromes, increase growth hormone levels, or increase GHSR activity.