Furthermore, s.c. administration deliversinsulin with suboptimal pharmacokinetics (PK) and pharmacodynamics(PD), which contribute to risks of side effects from long-term useof insulin injections, including hypoglycemia, peripheral hyperinsulinemia, lipodystrophy, weightgain, and hypoglycemia-associated autonomicfailure (HAAF). Therefore, oral insulinhas been considered as a paradigm-shifting solution in diabetes managementfor decades. Here, INS is linked to diabetes mellitus.