A Clinical Review of Concentrated Insulins for Type 1 and Type 2 Diabetes Mellitus

Insulin therapy is cornerstone treatment for the management of type 1 diabetes mellitus and often, is initiated for patients with type 2 diabetes inadequately controlled with oral antidiabetic medications or with severe hyperglycemia.  Concentrated insulin products are available to address the volume concerns with high doses of insulin U-100 (100 units per milliliter) due to poor or unpredictable absorption.  Humulin R U-500 has been available for 20 years, but have been underutilized in clinical practice due to conversions into a U-100 syringe or tuberculin syringe with the vial.  Now, its use may increase as a pre-filled pen and U-500 syringe has recently become available.  In addition, two additional concentrated insulin were approved in 2015 - insulin glargine U-300 (300 units per milliliter) and insulin degludec U-200 (200 units per milliliter).  These specific products are alternative insulin options for type 1 or type 2 diabetes, especially among patients with high doses of insulin therapy and high risk of hypoglycemia.  Insulin glargine U-300 and insulin degludec U-200 have similar A1c reduction to active comparators, but have a lower risk of hypoglycemia and nocturnal hypoglycemia.  This article evaluates and summarizes the indications, dosing, recent clinical evidence and role of insulin regular U-500, insulin glargine U-300 and insulin degludec U-200 for type 1 and type 2 diabetes mellitus.