OBJECTIVE -Both rapid-acting insulin analogs, insulin aspart and lispro, attenuate prandial glucose excursion compared with human soluble insulin. This trial was performed to study the pharmacokinetic and pharmacodynamic profiles of insulin aspart and insulin lispro in type 1 diabetic patients in a direct comparison and to investigate whether the administration of one analog results in favorable effects on prandial blood glucose control. RESEARCH DESIGN AND METHODS-A total of 24 type 1 diabetic patients (age 36 Ϯ 8 years, 16 men and 8 women, BMI 24.3 Ϯ 2.6 kg/m 2 , diabetes duration 17 Ϯ 11 years, HbA 1c 7.9 Ϯ 0.8%) on intensified insulin therapy were recruited into a single-center, randomized, double-blind, two-period, cross-over, glucose clamp trial. The subjects were given an individual need-derived dose of prandial insulin lispro or aspart immediately before a standard mixed meal.RESULTS -With respect to blood glucose excursions from time 0 to 6 h (Exc glu(0 -6 h) ) and from time 0 to 4 h (Exc glu(0 -4 h) ), the pharmacodynamic effect of insulin aspart and insulin lispro can be declared equivalent. This was supported by comparison with maximum postprandial blood glucose excursions (C max(glu) glu(0 -6 h) , Exc glu(0 -4 h) , and C max(glu) , respectively). For pharmacokinetic end points (maximum postprandial insulin excursions and area under the curve for insulin from time 0 to 6 h and from time 0 to 4 h), equivalence was indicated. No difference concerning absorption or elimination for time to maximal insulin concentration, time to half-maximum insulin concentration, and time to decrease to 50% of maximum insulin concentration was observed.CONCLUSIONS -These data suggest that in type 1 diabetic patients, both insulin analogs are equally effective for control of postprandial blood glucose excursions. Diabetes Care 25:2053-2057, 2002I n accordance with the results of the Diabetes Control and Complication Trial, near-normoglycemic blood glucose levels prevent the onset or delay the progression of long-term complications in type 1 diabetes (1). To mimic the physiological insulin secretion profile, intensified insulin therapy with unmodified human soluble insulin is performed as standard treatment regimen by a majority of patients (2,3). However, postprandial blood glucose peaks and excursions are not comparable with nondiabetic subjects. Absorption of unmodified insulin from the injection site is a complex process affected by only partially changeable factors, such as anatomic area, blood flow, injection volume, concentration of insulin, and possible local degradation process (4 -6). Therefore, considerable attention has been devoted to the development of insulin molecules with accelerated absorption kinetics (7-9). This more physiological profile of these shortacting insulin analogs leads to reduced prandial glucose excursions (10 -13). In well-controlled type 1 diabetic patients, postprandial administration of insulin aspart and insulin lispro has shown to be at least as effective as mealtime application o...

Injection of NN304 at different doses resulted in an increase in total NN304 concentration in a linear dose-response effect and a more even metabolic effect than NPH-insulin. However, we found no clear dose-response in its metabolic effect.

Under these study conditions, IAsp improved treatment satisfaction and quality of life regarding diet restrictions when compared with human insulin. The 'numbers needed to treat' for important quality of life benefits indicate that the effect of IAsp in this regard is not trivial.

NN304 is a long-acting insulin analogue that is acylated with a 14-C-fatty acid chain. Protraction of action of this novel insulin analogue is due not to slow absorption after subcutaneous administration but to reversible binding to albumin. We investigated the pharmacokinetic and pharmacodynamic properties of insulin analogue NN304 (0.3 and 0.6 U/kg) in comparison to NPH insulin (0.3 and 0.6 IU/kg) in 10 healthy volunteers performing a randomised, double-blind, cross-over, placebo-controlled glucose clamp study. During the observation period of 24 hours the areas under the insulin curve for NPH[0.3 IU/kg] vs. NPH[0.6 IU/kg] were 60 vs. 102 nmol min l(-1) (p<0.01) and for insulin analogue NN304[0.3 U/kg] vs. NN304[0.6 U/kg] 490 vs. 932 nmol min l(-1) (p <0.001), suggesting a clear dose-response relationship for both NPH insulin and NN304. The amount of disposed glucose (area under the curve of glucose infusion) differed with statistical significance between the five treatments and was highest with NPH[0.6 IU/kg] (2671 mg/kg) and lowest with placebo (265 mg/kg). However, area under the curve of glucose infusion after treatment with NN304 was only 36% (dose of 0.3 U/kg) and 24% (dose of 0.6 U/kg) of that observed with corresponding doses of NPH insulin. Moreover, increasing dosages of NN304 failed to demonstrate a significant dose-response with regard to the area under the curve of glucose infusion. This study demonstrates that the principle of protracted insulin action of NN304 by reversible binding to albumin is effective in humans albeit at a much lower rate of glucose utilisation when compared to NPH insulin. Thus, in contrast to animal studies NN304 and NPH insulin can not be considered equipotent in humans.