Mazen Alsahli, James R Thrasher and John E Gerich
Optimizing the treatment of people with diabetes relies on balancing the benefits of glycemic control with the risk of hypoglycemia. Although insulin is essential for treating patients with type 1 diabetes mellitus (T1DM), patient and physician concerns regarding an increased risk of hypoglycemia can lead to delays in initiating insulin treatment in patients with type 2 diabetes mellitus (T2DM). This clinical inertia contributes to reduced glycemic control and poorer outcomes for patients. Advances in insulin agents have reduced the risk of hypoglycemia. In particular, the introduction of insulin glargine, the first basal analog insulin with a 24-hour glucose-lowering profile with no pronounced peak, represented a significant step towards achieving this goal. To further improve patient management, a number of insulin formulations and molecules are in development and are designed to have pharmacokinetic/pharmacodynamic (PK/PD) profiles allowing closer mimicking of normal physiologic insulin release. Here we review these new agents, and discuss their hypoglycemic risk as reported in clinical trials. In addition, the difficulties in making comparative evaluations from studies with different patient populations and definitions of hypoglycemia are discussed. Solutions to improve future clinical trials are suggested. In general, the improved PK/PD profiles of new generation insulins appear to result in better clinical outcomes in terms of hypoglycemia. What is needed are head-to-head trials using standardized methods and criteria to allow clinicians to compare hypoglycemia rates between insulins, and help them to discuss appropriate choices of therapy with their patients.