Intramuscular versus subcutaneous injection of soluble and lispro insulin: comparison of metabolic effects in healthy subjects.

The aim of this study was to compare the glucodynamic effects of soluble insulin and the rapid acting insulin analogue insulin lispro after subcutaneous (s.c.) and intramuscular (i.m.) injection. Twelve healthy male volunteers (age 26.8 +/- 1.7 years, BMI 23.2 +/- 2.3 kg m(-2); mean +/- SD) participated in this single-centre, open-labelled, euglycaemic glucose clamp study on four different days. Soluble insulin or insulin lispro (0.2 U kg(-1)) were injected s.c. or i.m. into the thigh by syringe. The glucodynamic effects were assessed by registering the glucose infusion rates necessary to maintain blood glucose at 5.0 mmol l(-1) for the subsequent 420 min. Intramuscular injection of soluble insulin led to an earlier peak of metabolic action when compared to s.c. administered soluble insulin (tmax 138 +/- 29 vs 179 +/- 34 min; p < 0.05). The maximal metabolic effect and metabolic activity during the first 2 h after i.m. and s.c. injection of soluble insulin were comparable (GIRmax 9.7 +/- 2.3 vs 7.8 +/- 2.3 mg kg(-1) min(-1); n.s., AUC0-120min 0.60 +/- 0.18 vs 0.50 +/- 0.15 g kg(-1) 120 min; n.s.). Subcutaneous administration of insulin lispro led to a metabolic effect resembling that induced by i.m. application of soluble insulin (tmax 116 +/- 26 vs 138 +/- 29 min; n.s., GIRmax 11.1 +/- 2.3 mg vs 9.7 +/- mg kg(-1) min(-1); n.s.). However, the overall metabolic response during the first 2 h after injection was higher with s.c. insulin lispro (AUC0-120min 0.81 +/- 0.26 vs 0.60 +/- 0.18 g kg(-1) 120 min; p < 0.05). The glucodynamic activity of i.m. applied insulin lispro was comparable to that of lispro s.c.. Following i.m. injection of soluble insulin, the metabolic activity peaked more rapidly than with s.c. administration. In contrast, the metabolic effect of insulin lispro was similar with either route. The time-action profile of i.m. injected soluble insulin lies between that of s.c. applied soluble insulin and insulin lispro.