Abstract (Full Article PDF)

OBJECTIVE Clamp studies have shown that the absorption and action of rapid-acting insulin are faster with injection by a jet injector than with administration by conventional pen. To determine whether these pharmacokinetic changes also exist in patients with diabetes and benefit postprandial glucose control, we compared the pharmacologic profiles of insulin administration by jet injection versus conventional insulin pen after a standardized meal in patients with type 1 or type 2 diabetes.

RESEARCH DESIGN AND METHODS In a randomized, double-blind, double-dummy crossover study, 12 patients with type 1 diabetes and 12 patients with type 2 diabetes received insulin aspart either by jet injection or by conventional pen, in both cases followed by a standardized meal. Blood was sampled for 6 h for determination of glucose and insulin levels to calculate pharmacologic profiles.

RESULTS Insulin administration by jet injection resulted in shorter time until peak plasma insulin level (51.3 ± 6.4 vs. 91.9 ± 10.2 min; P = 0.003) and reduced hyperglycemic burden during the first hour (154.3 ± 20.8 vs. 196.3 ± 18.4 mmol · min · L−1; P = 0.041) compared with conventional administration. Jet injection did not, however, significantly reduce the hyperglycemic burden during the 5-h period thereafter. There was no indication that the jet injector performed differently in patients with type 1 and type 2 diabetes.

CONCLUSIONS The considerably more rapid insulin absorption after administration by jet injector translated to a significant if modest decrease in postprandial hyperglycemia in patients with type 1 and type 2 diabetes. The improved early postprandial glucose control may specifically benefit patients who have difficulty in limiting postprandial glucose excursions.

The pharmacologic profile of rapid-acting insulin analogs, although considerably faster than regular insulin, is still relatively slow compared with the profile of endogenous insulin release. As a consequence, patients with type 1 diabetes or insulin-requiring type 2 diabetes who use these analogs still face the risk of immediate postprandial hyperglycemia and late postprandial hypoglycemia. In particular, postprandial hyperglycemia has been recognized as an important contributor to suboptimal glucose control (1), which may explain why the introduction of rapid-acting analogs has had little effect on HbA1c in people with diabetes (2). Some have therefore suggested that these analogs should be injected at least 15 min before meals (3); however, this seems impractical to implement in daily practice.

Poor adherence to insulin therapy because of injection-related anxiety may be another, often neglected, reason for failure to reach glycemic targets with current rapid- and long-acting insulin analogs (4). A sizable proportion of insulin users admit to at least occasionally skipping insulin injections or restricting the number of daily injections (4). Although true needle phobia is rare, many patients with diabetes perceive insulin injections as painful or experience some form of anxiety with injections (5,6), the presence of which is strongly associated with nonadherence and poorer glycemic control (7).

Jet injectors for insulin administration provide a needle-free alternative to the use of pens or syringes and were originally developed for patients with needle phobia. Administration by jet injection significantly accelerates absorption of rapid-acting insulin from the subcutaneous area into the systemic circulation (8). Jet injectors deliver insulin at a high velocity (typically >100 m/s) directly across the skin in the subcutaneous tissue and dispense the insulin over a larger area than does injection by syringe (9). With the euglycemic clamp technique, we recently showed in healthy volunteers that administration of insulin aspart by jet injection reduced both the time until peak plasma insulin levels and the time to maximal glucose-lowering effect by approximately 50% when compared with insulin administered by conventional insulin pen (10).

Although the euglycemic clamp technique is a reliable method to investigate the pharmacodynamics of therapeutic insulin, it cannot be used to predict the glucose-lowering effect of insulin when injected before a meal, particularly in patients with diabetes. The aim of the current study was therefore to investigate the pharmacology of insulin injected by jet injector before a standardized meal in patients with type 1 diabetes and insulin-requiring type 2 diabetes. We also wanted to investigate whether patients would perceive insulin administration with the current jet injector device as more or less painful as insulin injection by pen.