Twice-daily biphasic insulin aspart 30 versus biphasic human insulin 30: a double-blind crossover study in adults with type 2 diabetes mellitus.
OBJECTIVE
The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart (BIAsp 30) with the equivalent premixed biphasic human insulin (BHI 30), administered twice daily, in patients with type 2 diabetes mellitus.


METHODS
In this randomized, double-blind, crossover trial, 13 patients (mean age, 64 years; baseline mean glycosylated hemoglobin, 7.7%; mean body mass index, 28.1 kg/m2) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast. At the end of each 2-week treatment period, 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays. All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance.


RESULTS
Total daily insulin exposure was similar between treatment periods. Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17% greater than that of BHI 30 after dinner and 44% greater after breakfast; both differences were statistically significant. The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner (18%) and breakfast (35%). Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group; differences were significant only after breakfast. The mean daily prandial glucose excursion was significantly lower for BIAsp 30 (16.2 mmol x h x L(-1)) than BHI 30 (17.9 mmol x h x L(-1)). Postprandial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast, but were significantly greater after lunch. Mean 24-hour and nocturnal serum glucose concentrations were similar, and both insulins were associated with < or = 7 minor and no major hypoglycemic events.


CONCLUSIONS
Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postprandial glucose excursions. This effect may be of importance when improvement in postprandial glucose control is desired.
McSorley
Paul T
PT
Department of Anaesthesia, Altnagelvin Area Hospital, Londonderry, Northern Ireland.
Bell
Patrick M
PM
Jacobsen
Lisbeth Vestergård
LV
Kristensen
Allan
A
Lindholm
Anders
A
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D061265:Biphasic Insulins; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061267:Insulin Aspart; D007336:Insulin, Isophane; D008297:Male; D008875:Middle Aged
D061265:Biphasic Insulins; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C557564:insulin aspart, insulin aspart protamine drug combination 30:70; D007336:Insulin, Isophane; D061267:Insulin Aspart