A Nature paper from DiMarchi, Tschöp, and colleagues describes a unimolecular conjugate combining a GLP-1R/GIPR co-agonist peptide with the pan-PPAR agonist lanifibranor through a pH-sensitive linker. After receptor internalization, the linker cleaves and the small-molecule payload escapes to the nucleus while the peptide continues signaling at the membrane. In obese diabetic mice, the conjugate outperformed peptide alone.