Clinical Challenges With Concentrated Insulins: Setting the Record Straight

The availability of insulins with concentrations greater than the standard 100 units/mL (U-100) concentration (adopted in the United States in 1973) provides additional options for managing diabetes, but these agents may be a source of confusion for many clinicians. Our awareness of such confusion has come about after a number of inquiries from health care providers (HCPs) to Lilly Diabetes, U.S. Medical Affairs, and inaccuracies in recent articles and published guidance. The purpose of this editorial is to bring attention to some of the more common and crucial issues and provide relevant background and clinical evidence to address and clarify misunderstandings and instruct HCPs on the safe and appropriate use of these agents. Four concentrated insulins are available in the United States. Three are analog insulins, which have been approved in the past 2–3 years: insulin glargine 300 units/mL (IGlar300) (1), insulin degludec 200 units/mL (IDeg200) (2), and insulin lispro 200 units/mL (ILis200) (3). The fourth, human regular insulin 500 units/mL (U-500R) (4), has been commercially available since 1997. These agents have diverse pharmacokinetic/pharmacodynamic (PK/PD) profiles and were developed to address different challenges of insulin therapy (5). Designing a basal insulin with stable, prolonged action was the rationale for IGlar300 (6). Insulin degludec was also developed as a longer-acting basal agent; the concentrated formulation (IDeg200) may benefit patients with higher insulin requirements (7). The more stable and protracted time-action profile for IGlar300 and insulin degludec (both 100 and 200 units/mL) supports once-daily dosing and may result in reduced hypoglycemia compared to insulin glargine 100 units/mL (IGlar100) (6–18). Rapid-acting prandial ILis200 is delivered in half the volume of the corresponding U-100 formulation, allowing a twofold increase in device capacity (19) and resulting in a longer-lasting pen. U-500R is a prandial/basal agent intended specifically for patients with severe insulin resistance …