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Tirzepatide, a dual receptor agonist of glucosedependent insulinotropic polypeptide and glucagonlike peptide1, enhances betacell survival and maintenance markers in obese diabetic ovariectomized mice

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Several substitutions particularly those with positive charges at p7 and p8 (AK, AR, KY and RY) diminished KIR2DS1 but not KIR2DL1 binding, consistent with KIR2DS1 being a more peptide-selective receptor than KIR2DL1 [6]

I see it appear suddenly and unpredictably in both new starters and long-term users, suggesting multiple overlapping mechanisms are usually at play rather than a single isolated cause