OBJECTIVE To assess the effect of mixing the insulin analog lispro (Humalog) with NPH (Humulin I) before injection on lispro's fast, short action profile.

RESEARCH DESIGN AND METHODS A total of 12 healthy volunteers received subcutaneous abdominal injections of 0.1 U/kg regular insulin and 0.2 U/kg NPH insulin as follows: lispro and NPH injected separately (treatment group A), lispro and NPH mixed in the syringe up to 2 min before single injection (treatment group B), and human regular insulin and NPH mixed and injected as in group B (treatment group C), on separateoccasions, in random order. Plasma glucose was maintained for 12 h by intravenous 20% glucose. Pharmacokinetic and pharmacodynamic parameters were compared by analysis of variance for repeated measures

RESULTS Peak plasma insulin levels (2.6 ± 0.8 vs. 2.2 ± 0.6 vs. 1.9 ± 0.6 ng/ml, P = 0.075),total glucose infused (121.5 ± 32.8 vs. 135.0 ± 49.0 vs. 117.3 ± 39.9 mg · kg⁻¹ · min⁻¹ P = 0.53), and maximum glucose infusion rate (GlR_max) (8.3 ± 0.9 vs. 8.0 ± 1.7 vs. 7.1 ± 2.4 mg · kg⁻¹ · min⁻¹ P = 0.65) were not significantly different between treatments. The times until peak insulin concentrations were similar in treatment groups A and B, but significantly shorter than in treatment group C (0.9 ± 0.3 and 1.2 ± 0.2 vs. 2.0 ± 0.4 h, respectively, P = 0.042). The times until GIR_max were also not different (113.9 ± 41 and 122.0 ± 45 vs. 209.0 ± 51.3 min, , respectively, P = 0.002). The glucose infusion rate (GIR) then fell to 50% GIRmax more quickly in treatment groups A and B than in treatment group C (239.9 ± 40.5 vs. 292.4 ± 133.3 vs. 399.5 ± 78.3, respectively, P = 0.005).

CONCLUSIONS The action profile of lispro is not attenuated by mixing lispro with NPH in the syringe immediately before injection. The advantages are available to those individuals who need to combine typesof insulin before injection to achieve optimal diabetes control.