Rapid and long-acting analogues as an approach to improve insulin therapy: an evidence-based medicine assessment

This review summarizes the results of clinical trials with the currently available insulin analogues (i.e., insulin lispro, insulin aspart, and insulin glargine) and evaluates their clinical benefit applying the standards of evidence-based medicine. All analogues show a more physiological time-action profile with either a shorter onset and shorter duration of action (insulin lispro and insulin aspart) or a more constant effect lasting at least 24 hours (insulin glargine). These advantages in the time-action profiles have been shown to improve various surrogate parameters (e.g., postprandial blood glucose concentrations) in a number of randomized controlled trials. Only a few studies are available, however, demonstrating a benefit on patient-oriented clinical endpoints as decrease in glycated hemoglobin (HbA(1c)), reduction of hypoglycemic episodes, and improvement in quality-of-life. This review focuses on the impact of the use of insulin analogues on these endpoints. Provided that insulin therapy is optimized as a whole (rather than just switching from human insulin to insulin analogues) all 3 analogues show (modest) beneficial impact on these endpoints. Finally, we review the relevant data concerning the safety aspects of the various analogues, thus allowing the reader to perform an individual risk-benefit-assessment.