Elucidating the mechanism
The impact of niacinamide was assessed in pharmacokinetic analyses in pigs and humans, small angle X-ray scattering experiments, trans-endothelial transport assays, vascular tension measurements, and subcutaneous blood flow imaging.
Niacinamide increased the rate of early insulin aspart absorption in pigs, and pharmacokinetic modelling revealed this effect to be most pronounced up to ~30–40 min after injection in humans.
Niacinamide increases the initial abundance of insulin aspart monomers and transport of insulin aspart after subcutaneous administration, and also mediates a transient, local vasodilatory effect.
By reducing the tendency to remain self-associated as hexamers after subcutaneous administration, the speed of absorption into the circulation is increased, and insulin aspart reaches peak plasma concentrations more rapidly compared with RHI, to better mimic the normal mealtime insulin response ().
Nevertheless, despite such advances in insulin development, many patients with type 1 diabetes (T1D) or insulin-dependent type 2 diabetes (T2D) remain unable to control postprandial hyperglycemia and hence meet or maintain Hb A).
The oligomerization of insulin is partly driven by hydrophobic interactions, as the thermodynamically favorable shielding of hydrophobic residues plays an important role in formation of the insulin hexamer.
Niacinamide and many of its derivatives belong to a group of compounds classified as hydrotropes ().