The present invention relates to insoluble compositions comprising a
protein selected from the group consisting of insulin, insulin analogs,
and proinsulins; a derivatized protein selected from the group consisting
of derivatized insulin, derivatized insulin analog, and derivatized
proinsulin; a complexing compound; a hexamer-stabilizing compound; and a
divalent metal cation. Formulations of the insoluble composition are
suitable for both parenteral and non-parenteral delivery for treating
hyperglycemia and diabetes. Microcrystal forms of the insoluble
precipitate are pharmaceutically analogous to the neutral protamine
Hagedorn (NPH) insulin crystal form. Surprisingly, it has been discovered
that suspension formulations of such insoluble compositions possess unique
and controllable dissolution properties that provide therapeutically
advantageous glucodynamics compared with insulin NPH formulations.