The pharmacokinetic and pharmacodynamic properties of different formulations of biphasic insulin aspart: a randomized, glucose clamp, crossover study.
BACKGROUND
Type 2 diabetes patients on premixed insulin are commonly prescribed biphasic insulin with low prandial insulin content, such as biphasic insulin aspart (BIAsp) 30, comprising 30% insulin aspart (IAsp). The new formulations BIAsp 50 and BIAsp 70 contain 50% and 70% soluble IAsp, respectively. We compared the pharmacodynamics (PD) and pharmacokinetics (PK) of BIAsp 30, 50, and 70 and IAsp in a glucose clamp trial.


METHODS
In this randomized, double-blind, crossover study at a clinical research institute, 32 type 1 diabetes patients on basal-bolus therapy each underwent four glucose clamps (clamp level 5 mmol/L, duration 28 h post-dosing [12 h for IAsp]) and received a single dose of 0.4 U/kg BIAsp 30, 50, or 70 and IAsp. Main PD/PK outcome parameters measured were early- and late-phase glucose disposal (area under the curve of glucose infusion rate [AUC(GIR)]), nonesterified fatty acid concentrations, and IAsp concentrations.


RESULTS
With increasing proportions of soluble IAsp, the insulin formulations showed significantly higher early metabolic activity (ratio of AUC(GIR) 0-6 h: BIAsp 50/BIAsp 30 = 1.28 [P < 0.001], BIAsp 70/BIAsp 50 = 1.18 [P < 0.001), IAsp/BIAsp 70 = 1.15 [P < 0.01]) and lower late metabolic activity (ratio of AUC(GIR) 12-28 h: BIAsp 50/BIAsp 30 = 0.17 [P < 0.01], BIAsp 70/BIAsp 50 = 0.21 [P < 0.05]). Likewise, early IAsp levels were significantly greater and late PK concentrations were significantly lower with increasing proportion of soluble IAsp.


CONCLUSIONS
There are significant differences between the early and late PD and PK effects among BIAsp 30, 50, and 70 and IAsp that should allow tailored treatment with the convenience of prandial and basal insulin in each injection.
Heise
T
T
Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany. tim.heise@profil-research.de
Eckers
U
U
Kanc
K
K
Nielsen
J N
JN
Nosek
L
L
D000328:Adult; D019540:Area Under Curve; D061265:Biphasic Insulins; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004311:Double-Blind Method; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D061267:Insulin Aspart; D007336:Insulin, Isophane; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D061265:Biphasic Insulins; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; D007336:Insulin, Isophane; C557564:insulin aspart, insulin aspart protamine drug combination 30:70