Frontiers in Drug Discovery (April 10): "Beyond GLP-1" Review Maps Underexplored Peptide-Receptor Systems as Next Therapeutic Frontier
A Frontiers in Drug Discovery review (April 10, 2026) catalogs underexplored peptide-receptor systems that the authors argue failed not for biological reasons but because of technical and conceptual barriers solvable with modern peptide engineering. Coverage spans metabolic and energy-balance peptides (apelin, spexin), appetite-regulating systems (peptide YY, oxyntomodulin), bone-muscle-fat crosstalk mediators (osteocalcin, irisin), and neuroendocrine-immune-metabolic peptides (phoenixin, relaxin-3). The argument: lessons from GLP-1 — stabilization, conjugation, and dosing innovation — now make these orphan receptor systems tractable. Companion essay from Bloomgarden in the Journal of Diabetes (2026, vol 18 e70204) frames the same opportunity from the clinical side, citing GLP-1 tolerability ceilings and the 10-20% non-responder problem that creates room for the next wave.