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Native human amylin shows amyloidogenic propensity (Aβ-like fibril formation in diabetic pancreatic islets) requiring stabilising modifications: cagrilintide incorporates (1) Pro25, Pro28, Pro29 substitutions (inherited from pramlintide) blocking β-sheet propensity and fibrillisation, (2) an Arg18 substitution improving solubility, and (3) a C20 diacid acylation (eicosanedioic acid) on Lys8 via γ-Glu/OEG linker, conferring reversible plasma albumin binding responsible for its exceptional half-life (~180 hours, compatible with weekly administration)