Pharmacodynamics of 100 vs. 200 Units of U500 Regular Insulin in Obese Subjects with T2DM

Practitioners often consider using U500 regular insulin (U500) in obese patients with T2DM who take >100 units of insulin/day. To compare the pharmacodynamic effects of 2 doses of U500 in such patients, we did a randomized double blind cross over study in which 100 or 200 units (U) SQ of U500 was given once and IV glucose was then given as necessary to maintain euglycemia (EU). Subjects stopped their own insulin at least 12 hours before the U500 dose and were kept on an insulin drip overnight to target EU. Subjects were NPO for 8 hours before and 4 hours after U500 dosing. Meals with 30 gm of carbohydrate were given at hours 4, 9, 13, 26, 30. Rate of U500 onset was determined by measuring the area under the curve (AUC) of IV glucose given hours 0-4, the peak infusion rate achieved hours 0-4, and the time at which IV glucose was started. Duration of action was determined by measuring the time IV glucose was required to maintain EU. The effect of the each dose on glucose lowering was determined by measuring the AUC of the IV glucose given to maintain EU for the entire study. 3F, 9M completed the study (age 54 ± 5 years, BMI 36.0 ± 3.3 kg/m², total daily insulin dose 174 ± 40 units, mean ± SD).

We conclude the duration of action of U500 is longer following administration 200 vs. 100. However, no differences were found in rate of onset or total amount of glucose required to maintain EU. Future studies should examine the pharmacodynamics of repeated doses of U500 in similar subjects.