Variability of Insulin Action and Clinical Effects

Abstract

It is now generally accepted that insulin treatment regimens matching normal physiologic insulin secretion are the optimal approach to management of patients with diabetes whose glycemia cannot be controlled with lifestyle changes or oral drugs. However, many patients do not receive the full benefits of such therapy because of variability in the action of older insulin formulations. Within-patient variability in the pharmacodynamic and pharmacokinetic profiles of older insulin preparations makes it difficult to achieve glycemic control, increases the risk of hypoglycemia, and contributes to day-to-day variability in blood glucose, which is now recognized as an independent risk factor for long-term complications of diabetes. The newer insulin analogs have been engineered to provide more consistent and predictable pharmacodynamic and pharmacokinetic profiles and have been shown to result in significantly decreased within-patient variability in plasma glucose. These newer insulin analogs can also be titrated more aggressively, with less risk of hypoglycemia, and they facilitate the development of insulin regimens that more effectively mimic physiological insulin secretion. In the effort to achieve good glycemic control and lower glycosylated hemoglobin levels, it is imperative that clinicians fully understand the pharmacodynamic and pharmacokinetic actions of insulin analogs to use them effectively.