Insulin glulisine, insulin lispro and regular human insulin show comparable end-organ metabolic effects: an exploratory study.
OBJECTIVE
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/m(2), haemoglobin A(1c) 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 (S(EGP)) 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 S(EGP) (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 S(EGP), GU, FFA, glycerol and lactate levels, providing evidence for similar end-organ metabolic effects.
Horvath
K
K
Department of Internal Medicine, Medical University of Graz, Graz, Austria. karl.horvath@klinikum-graz.at
Bock
G
G
Regittnig
W
W
Bodenlenz
M
M
Wutte
A
A
Plank
J
J
Magnes
C
C
Sinner
F
F
Fürst-Recktenwald
S
S
Theobald
K
K
Pieber
T R
TR
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D005990:Glycerol / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007328:Insulin / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D061268:Insulin Lispro; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D019344:Lactic Acid; C479079:insulin glulisine; D005990:Glycerol