INS and type 2 diabetes mellitus: In the clinical trial, 325 severely insulin-resistant patients with type 2 diabetes on high-dose U-100 insulin (>200 units of insulin/day) with or without oral antihyperglycemic agents were randomized to receive U-500R thrice daily (TID) or twice daily (BID), which was initiated and titrated over a 24-week period in place of U-100 insulins [3].