Comparison of thrice daily 'high' vs. 'medium' premixed insulin aspart with respect to evening and overnight glycaemic control in patients with type 2 diabetes (original) (raw)
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Clinical Therapeutics, 2002
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. 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. 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. 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.
Diabetes, Obesity and Metabolism, 2006
Aim: The aim of this study was to compare the effect of multiple mealtime injections of biphasic insulin aspart 30 (30% fast-acting insulin aspart in the formulation, BIAsp30) to traditional basal-bolus human insulin regimen (HI) on glycaemic control in patients with type 1 diabetes. Methods: Twenty-three patients (eight women and 15 men) aged 44.8 (20.6-62.5) years (median and range) with a diabetes duration of 19.5 (1.6-44.6) years completed the study. All eligible patients were randomly assigned to BIAsp30 thrice daily supplied with bedtime NPH insulin when necessary, or basal-bolus HI for 12 weeks and then switched to the alternative regimen for another 12 weeks. The insulin dose adjustments were made by patients on the basis of advice from a diabetes nurse. At end of each treatment period, the patients attended two profile days, 1 week apart for pharmacodynamic and pharmacokinetic assessments. HbA 1C was measured at baseline and at the end of each treatment period. A seven-point self-monitored blood glucose (SMBG) was obtained twice weekly. Results: In comparison with HI, multiple mealtime injections of BIAsp30 resulted in a significant reduction in HbA 1C [HI vs. BIAsp30 (%, geometric mean and range): 8.6 (7.4-11.4) vs. 8.3 (6.7-9.8), p ¼ 0.013]. During treatment with BIAsp30, nighttime glycaemic control was significantly improved. Day-to-day variation in pharmacodynamics and pharmacokinetics and the rate of hypoglycaemia were not increased with BIAsp30 compared with HI. Conclusions: In type 1 diabetics, multiple mealtime administration of BIAsp30 compared with traditional basalbolus human insulin treatment significantly improves long-term glycaemic control without increasing the risk of hypoglycaemia. Despite a higher proportion of intermediate-acting insulin, thrice-daily injections with BIAsp30 do not increase the day-to-day variations in insulin pharmacokinetics and pharmacodynamics.
Diabetes, Obesity and Metabolism, 2009
Aim: To evaluate clinical efficacy and safety of biphasic insulin aspart (BIAsp) 30 twice daily (b.i.d.) vs. BIAsp 50 or BIAsp 70 (high-mix regimens) thrice daily (t.i.d.) all in combination with metformin in a 36-week clinical trial in subjects with type 2 diabetes. Methods: Efficacy measurements included haemoglobin A 1c (HbA 1c ) and eight-point plasma glucose (PG); safety included adverse events (AEs) and hypoglycaemic episodes. The three treatment groups (approximately 200 subjects in each group) were well matched regarding sex ratio, ethnicity, age and body mass index. Results: After 12 weeks, 43% and 54% in the BIAsp 50 and 70 groups, respectively, switched their dinner insulin to BIAsp 30. Both high-mix regimens were non-inferior to BIAsp 30 b.i.d., as measured by change in HbA 1c , and the BIAsp %50 regimen was superior. The odds for meeting the American Diabetes Association and The American Association of Clinícal Endocrinologist HbA 1c targets of <7% and 6.5%, respectively, were significantly higher with the BIAsp 50 regimen than with BIAsp 30. A significantly lower PG level was achieved from lunch until 02:00 hours with both high-mix regimens compared with BIAsp 30 b.i.d. AEs were mild or moderate with all three regimens. Frequency of hypoglycaemic episodes was comparable for the BIAsp 50 and the BIAsp 30 b.i.d. regimens but was significantly higher with BIAsp 70 t.i.d. Conclusions: Glycaemic control improved with BIAsp 50 t.i.d. without higher incidence of hypoglycaemia compared with BIAsp 30 b.i.d.; with BIAsp 70 t.i.d. lower PG levels from lunch to 02.00 hours, but more hypoglycaemic episodes were obtained compared with BIAsp 30 b.i.d. (Clinical Trials.gov ID no: NCT00184574).
Diabetes, Obesity and Metabolism, 2003
Objective: Biphasic insulin aspart 30 (BIAsp30) is a dual release formulation, containing 30% soluble and 70% protamine-crystallized insulin aspart. This study compared the glycaemic control and safety profiles achieved with either twice daily BIAsp30 or NPH insulin in patients with type 2 diabetes not optimally controlled by oral hypoglycaemic agents (OHAs), NPH insulin or a combination of both. Methods: In this 16-week multinational, parallel-group, double-blind trial, 403 such patients were randomized to receive either BIAsp30 or NPH insulin immediately before breakfast and evening meals. OHAs were discontinued at randomization. Efficacy was assessed by glycosylated haemoglobin (HbA 1c ) and self-recorded daily 8-point blood glucose (BG) profiles. Hypoglycaemic and other adverse events were the chosen safety parameters. Results: HbA 1c concentration decreased by >0.6% (p < 0.0001 vs. baseline) in both groups, with metabolic control continuing to improve throughout the trial without reaching a stable level. Patients who switched from once or twice daily NPH monotherapy to twice daily BIAsp30 achieved a significantly greater reduction in HbA 1c (0.78%) than those randomized to twice daily NPH insulin (0.58%; p ¼ 0.03). BIAsp30 decreased mean daily postprandial glycaemic exposure to a greater extent than NPH insulin (mean difference ¼ 0.69 mmol/l; p < 0.0001), reflecting greater decreases in the postbreakfast and postdinner increments (of 1.26 and 1.33 mmol/l, respectively), although postlunch increment was relatively increased (by 0.56 mmol/l). Despite the greater reduction in overall postprandial glycaemic exposure in the BIAsp30 group, the overall safety profile of BIAsp30 was equivalent to that of NPH insulin with <2% of patients experiencing major hypoglycaemia, and approximately 33% reporting minor hypoglycaemic episodes, in both groups. Conclusion: Twice daily BIAsp30 reduced postprandial glucose exposure to a significantly greater extent than NPH insulin and was at least as effective at reducing HbA 1c in patients with type 2 diabetes. Both insulins were well tolerated. In patients poorly controlled on OHAs or NPH alone, glycaemic control can be improved by switching to twice daily BIAsp30, without increasing hypoglycaemic risk.
Journal of Clinical Medicine
Aim: To compare in terms of glycemic variability two premixed insulins, Premixed Human Insulin 30/70 (PHI) and Biphasic Aspart 30 (BiAsp30), using Continuous Glucose Monitoring (CGM) and to estimate the correlation of Glycated Albumin (GA) and Fructosamine (FA) with CGM data. Patients-Data: A total of 36 well-controlled patients with type 2 Diabetes Mellitus (T2DM) underwent 7-day CGM with PHI and subsequently with BiAsp30. GA and FA were measured at the first and last day of each week of CGM. Results: BiAsp30 was associated with lower Average Blood Glucose (ABG) during the 23:00–03:00 period (PHI: 135.08 ± 28.94 mg/dL, BiAsp30: 117.75 ± 21.24 mg/dL, p < 0.001) and the 00:00–06:00 period (PHI: 120.42 ± 23.13 mg/dL, BiAsp30: 111.17 ± 14.74 mg/dL, p = 0.008), as well as with more time below range (<70 mg/dL) (TBR) during the 23:00–03:00 period in the week (PHI: 3.65 ± 5.93%, BiAsp30: 11.12 ± 16.07%, p = 0.005). PHI was associated with lower ABG before breakfast (PHI: 111.75 ± 23...
Diabetic Medicine, 2005
To compare pharmacokinetic characteristics of two biphasic insulin aspart (BIAsp) formulations: BIAsp30 and BIAsp70 (30% and 70%, respectively, of fast-acting insulin aspart) during 15 days of multiple dosing (thrice daily). Methods A total of 22 patients with Type 1 diabetes (nine women, 13 men) aged 41.4 ± 9.9 years (mean ± SD) with a diabetes duration of 18.9 (2.3-40.3) years (median and range) completed the randomized, double-blinded, two-period crossover study. On day 1 and day 15 of each treatment period, 24-h serum insulin and glucose profiles were evaluated. Total area under the insulin aspart concentrationtime curve (AUC (0−24 h) ), AUC after dinner administration stratified into early (AUC dinner(0−6 h) ) and intermediate-phase (AUC dinner(6−14 h) ), maximum insulin concentration (C max ), time to maximum insulin concentration (T max ) after each meal were recorded.
Diabetes Technology & Therapeutics, 2012
Background: We compared the pharmacokinetic and pharmacodynamic profiles of insulin aspart, biphasic insulin aspart 70 (BIAsp70) and 50 (BIAsp50) (containing 70% and 50% rapid-acting insulin aspart, respectively), and soluble human insulin under experimental conditions. Subjects and Methods: In this randomized, four-period crossover study, 19 type 1 diabetes patients received subcutaneous injections of identical doses (0.2 U/kg) of insulin aspart, BIAsp70, or BIAsp50 immediately before a standardized meal or human insulin 30 min before meal. Plasma glucose and serum insulin were measured for 12 h postprandially. Results: The pharmacokinetic and pharmacodynamic profiles of human insulin differed from those of insulin aspart, BIAsp70, and BIAsp50. The three different aspart preparations had easily distinguishable features with regard to onset and duration of action. Insulin aspart preparations were, on average, absorbed twice as fast as human insulin. In the initial phases (0-4 h and 0-6 h), the insulin area under the concentration-time curve (AUC ins) was significantly higher during insulin aspart treatment compared with the others, whereas insulin aspart had a significantly lower AUC ins over the last 6 h (P < 0.05). BIAsp70 and BIAsp50 provided insulin coverage comparable to that of human insulin over the last 6 h. Insulin aspart had the most pronounced onset of action and the shortest duration. Comparing with insulin aspart and BIAsp70, BIAsp50 revealed a closer treatment ratio to human insulin on pharmacodynamic end points. Conclusions: BIAsp70 and BIAsp50 injected immediately before a meal are at least as effective as human insulin injected 30 min earlier in controlling postprandial glycemic excursions. BIAsp50 showed the greatest similarity to human insulin with regard to pharmacokinetic and pharmacodynamic profiles.