Skip to Main Content
U-500R vs U-100..

+

As the prevalence of insulin resistance and obesity continue to rise, so does the need for higher doses of insulin in patients with type 2 diabetes.1,3 Obese patients with severe insulin resistance associated with diabetes generally require at least 2 units of insulin per kilogram (kg) or over 200 units of insulin daily to control blood glucose levels. Due to the high insulin demands, the use of regular U-500 insulin increased 97% between 2008 and 2010.2 Even with the increase in use, there have been limited studies on pharmacodynamic and pharmacokinetic properties of U-500 insulin, especially in obese patients at higher clinically used doses.

+

A prospective, single-center, four-period, four-sequence, crossover, randomized, double-blind study was conducted to evaluate the pharmacokinetic and pharmacodynamic profiles of healthy obese (BMI 30-40kg/m2; weight ≤125kg) subjects using human regular U-500 and regular U-100 insulin. The primary objective of the study was to evaluate the relative exposure for U-500R and U-100R after subcutaneous administration of 50 and 100 unit doses. Twenty four patients were enrolled in the study and randomly assigned to different dosing sequences of the 4 different insulin doses and formulations. The mean age of subjects was 39.6 years, with an average weight of 98.1kg and BMI of 34.4kg/m2. Subjects underwent euglycemic clamps for up to 24 hours using the Biostator automated glucose clamp device which automatically calculated the appropriate rate of a 20% glucose solution intravenous infusion to maintain the subject’s blood glucose concentrations within 5% of target. Serum immunoreactive insulin concentrations were measured at specific intervals throughout the clamp and analyzed for area under the serum insulin-time curve from zero to return to baseline (AUC0-t’), maximum serum insulin concentrations (Cmax), time of maximum serum insulin concentration (tmax) and apparent terminal half life (t1/2). The glucose infusion rates (GIR) were also analyzed for maximum GIR (Rmax), time of maximum GIR (tRmax), amount of glucose infused (Gtot), and times of half-maximum GIR before and after Rmax (early and late tRmax50).1

+

The mean insulin dose was 0.5 units/kg (0.4-0.6unit/kg) for subjects receiving 50 units of insulin and 1 unit/kg (0.8-1.3 units/kg) in those receiving 100 units of insulin. Both effects and exposure to insulin (Gtot and AUC0-t’) were similar between formulations at 50 and 100 unit doses. With U-500R, Cmax and Rmax were lower relative to the U-100R at both doses, while the tmax and tRmax were longer for U-500R, but only at the 100 unit dose demonstrating that the U-500R had a longer time-to-peak concentration and onset of action compared to U-100R. At both doses, the t1/2 was longer for U-500R (4.4-4.6hrs) compared to U-100R (3.3-3.9hrs).  Since the study found the half life of U-500 to be longer, the authors proposed that it could be dosed two to three times daily without the use of basal insulin. ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.