Insulin glulisine, insulin lispro and regular human insulin show comparable end-organ metabolic effects: an exploratory study

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Aims:  To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lispro) and regular human insulin (RHI) in patients with type 1 diabetes mellitus.

Methods:  Eighteen patients with type 1 diabetes mellitus (mean age 36.9 ± 8.6 years, BMI 23.6 ± 2.8 kg/m2, haemoglobin A1c 7.4 ± 0.9%) were randomized in this single-centre, double-blind, three-period cross-over, standard Latin-square, euglycaemic glucose clamp trial. Patients received sequential, primed stepwise intravenous infusions of glulisine, lispro or RHI (infusion rates were increased in a stepwise manner from an initial rate of 0.33 [180 min] to 0.66 [180 min] and 1.00 [180 min] mU/kg/min). The primary variables were the suppression of endogenous glucose production (SEGP) and glucose uptake (GU).

Results:  Mean basal endogenous glucose production (EGP) was 1.88, 2.12 and 2.12 mg/kg/min for glulisine, lispro and RHI respectively. Mean (±s.e.) maximum absolute SEGP (adjusted for basal EGP) was −1.64 ± 0.06, −1.72 ± 0.05 and −1.56 ± 0.05 mg/kg/min respectively. Mean (±s.e.) maximum absolute increase in GU (adjusted for basal GU) was 6.46 ± 0.26, 6.23 ± 0.24 and 6.72 ± 0.24 mg/kg/min respectively. There were no clinically relevant differences between the three insulin treatments with respect to serum insulin, free fatty acid (FFA), glycerol or lactate levels. No serious adverse events and no episodes of severe hypoglycaemia were reported.

Conclusions:  This study shows that glulisine, lispro and RHI have similar effects on SEGP, GU, FFA, glycerol and lactate levels, providing evidence for similar end-organ metabolic effects.

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