L. Heinemann et al., Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo, DIABET CARE, 23(5), 2000, pp. 644-649
OBJECTIVE - To study the pharmacodynamic properties of the subcutaneously i
njected long-acting insulin analog HOE901 (30 mu g/ml zinc) in comparison w
ith those of NPH insulin and placebo.
RESEARCH DESIGN AND METHODS- In this single-center double-blind euglycemic
glucose clamp study, 15 healthy male volunteers (aged 27 +/- 4 years, BMI 2
2.2 +/- 1.8 kg/m(2)) received single subcutaneous injections of 0.4 U/kg bo
dy wt of HOE901, NPH insulin, or placebo on 3 study days in a randomized or
der. The necessary glucose infusion rates (GIRs) to keep blood glucose conc
entrations constant at 5.0 mmol/l were determined over a 30-h period after
administration.
RESULTS - The injection of HOE901 did not induce the pronounced peak in met
abolic activity observed with NPH insulin (GIR(max) 5.3 +/- 1.1 vs. 7.7 +/-
1.3 mg . kg(-1) min(-1)) (P < 0.05); after an initial rise, metabolic acti
vity was rather constant over the study period. This lack of peak was confi
rmed by a lower glucose consumption in the first 4 h after injection (area
under the curve from 0 to 4 h [AUC(0-4) (h)] 1.02 +/- 0.34 vs. 1.48 +/- 0.3
4 g/kg) (P < 0.001) with HOE901, as compared with NPH insulin. In this sing
le-dose study, the metabolic effect measured over a period of 30 h was lowe
r with HOE901 than with NPH insulin (AUC(0-30 h) 7.93 +/- 1.82 vs. 9.24 +/-
1.29 g/kg) (P < 0.05).
CONCLUSIONS - This study shows that the soluble long-acting insulin analog
HOE901 induces a smoother metabolic effect than NPH insulin, from which a b
etter substitution of basal insulin requirements may follow.