Comparison of Premixed Human Insulin 30/70 to Biphasic Aspart 30 in Well-Controlled Patients with Type 2 Diabetes Using Continuous Glucose Monitoring (original) (raw)
Related papers
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.
Journal of diabetes investigation, 2011
Aims/Introduction: Biphasic insulin aspart 30 (BIAsp 30) has an earlier and stronger peak effect with a similar duration of action to biphasic human insulin 30 (BHI 30). However, direct comparison of daily glucose excursion during treatment with these two types of insulin has not been carried out. We carried out continuous glucose monitoring (CGM) and evaluated the 48-h glucose profile during twice-daily injections of BIAsp 30 or BHI 30 at the same dosage in 12 hospitalized patients with type 2 diabetes who participated in a randomized cross-over trial. The 48-h average glucose level and mean amplitude of glucose excursion (MAGE) were lower during BIAsp 30 treatment than with BHI 30. The average glucose level during 2-3 h after breakfast and 2-4 h after dinner, and the incremental postprandial glucose from just before to 4 h after dinner were lower with BIAsp 30 treatment than with BHI 30. Furthermore, BIAsp 30 treatment reduced the SD from 30 min before to 4 h after breakfast ...
Diabetes, Obesity and Metabolism, 2003
Background: The glycaemic control of thrice daily treatment with premixed biphasic insulin aspart (BIAsp) without other antidiabetic therapy was tested in type 2 diabetic patients, in order to compare the glucose control of a 'high' mixture (BIAsp 70) or a 'medium' mixture (BIAsp 50) (70 or 50% soluble IAsp and 30 or 50% protamine-crystallized IAsp, respectively) administered just before dinner. Aim: To compare these regimens to conventional 30 : 70 premixture on a twice a day basis. Methods: This randomized, double-blind, two-period crossover study included 16 patients with type 2 diabetes. Twenty four-hour serum glucose and insulin profiles were obtained thrice: (1) after a one-week run-in period with biphasic human insulin (BHI) 30/70 twice daily (run-in), (2) after 4 weeks of treatment with thrice daily BIAsp 70 before breakfast, lunch and dinner (Dinner70 regimen) and (3) after 4 weeks of BIAsp 70 before breakfast and lunch and BIAsp 50 before dinner (Dinner50). Results: Daytime average serum glucose was lower with Dinner70 compared to run-in (9.6 AE 0.39 mmol/l vs. 11.2 AE 0.61 mmol/l, p < 0.05). Postprandial glucose excursions after breakfast and lunch were lower, but fasting morning glucose was higher during the treatment periods than in the run-in period. Twenty four-hour C-peptide AUC was considerably lower during both treatment periods than in the run-in period (run-in/Dinner50 ratio 1.29 [1.08; 1.54] p < 0.01; run-in/Dinner70 ratio 1.31 [1.08;1.58], p < 0.01). Conclusions: Switching the dinner dose to BIAsp 50 did not alter overall glucose control significantly from that provided with BIAsp 70. Exploratory analyses between the two active treatment regimens and run-in/BHI indicate that thrice daily BIAsp 70 administration: (1) for optimization of the night-time control, the dinner dose needs adjustment or replacement by a premixed insulin with a larger proportion of basal insulin than BIAsp 50 and (2) none of the premixtures adequately provide for both the evening meal and overnight requirements.
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).
Clinical Diabetology, 2020
Background. Peaks and nadirs of blood glucose level varying daily in a person is referred to as glycemic variability (GV). GV associated with diabetics has been recently linked to cardiovascular disorders (CVD) or even chronic kidney disease (CKD) progression. Faster-acting insulin aspart is the latest ultra-rapid acting bolus insulin which has shown much lesser intra-and inter-patient variability as compared to conventional bolus insulin. Material and methods. However, inadequate data exist regarding GV in patients with advanced stages of CKD. Hence, with this objective, the present case study was undertaken with eight patients divided into two equal groups, wherein faster-acting insulin aspart and insulin aspart were used as the boluses, respectively. Continuous glucose monitoring data of the patients were taken for the initial four days to calculate mean amplitude of glycemic excursion (MAGE) of the total four days for each individual (mmol/L) to see the difference in GV. A value of > 3.607 mmol/L (65 mg/dL) was considered to be statistically significant. Results. In this case study of eight stage 4 CKD type 2 diabetic patients, statistically significant lower GV was observed in the faster-acting insulin aspart arm when compared with the insulin aspart arm. The pvalue was 0.0004 in unpaired t-test and < 0.05 for U in Mann-Whitney U test after ruling out the baseline confounding factors. Conclusions. This study confirms the stable pharmacokinetic and dynamic properties of faster-acting insulin aspart and subsequent studies with larger number of patients are required for a conclusive outcome. (Clin
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.
Diabetologia, 2006
Aims/hypothesis: The pharmacokinetic and pharmacodynamic properties of biphasic insulin aspart (BIAsp 30) (30% soluble, 70% protaminated insulin aspart [IAsp]) and insulin glargine (IGlarg) were compared. Methods: Twelve people with type 2 diabetes took part in two 24-h isoglycaemic clamp studies, 1 week apart. Patients were randomised to treatment with 0.5 U/kg of BIAsp 30 (0.25 U/kg at 08.30 h and 0.25 U/kg at 20.30 h) or 0.50 U/kg IGlarg at 08.30 h. Both insulins were given by subcutaneous injection into the anterior abdominal wall. The plasma glucose, glucose infusion rates, plasma insulin and C-peptide concentrations were measured. Results: All 12 patients were men; mean (±SD) age was 58.8 (8.9) years, BMI 31.0 (3.0) kg/m 2 and HbA 1c 7.1 (0.6)%. Plasma glucose was constant throughout the 24-h clamp period. After each injection of BIAsp 30, glucose infusion rates increased, reaching a distinct peak approximately 3-5 h after injection. A much flatter postinjection profile was observed following IGlarg administration. Plasma insulin concentrations rose rapidly after each injection of BIAsp 30, reaching a distinct peak after approximately 2-3 h. A flatter plasma insulin profile reached a plateau approximately 6-16 h after IGlarg administration. Plasma C-peptide fell below baseline after both injections of BIAsp 30 but remained unaltered after IGlarg injection. Conclusions/interpretation: The pharmacodynamic and pharmacokinetic profiles were 34 and 28%, respectively, higher following equivalent doses (0.5 U/kg) of BIAsp 30 given as two split doses than following IGlarg given as a single daily dose.
Long-term efficacy and safety of biphasic insulin aspart in patients with type 2 diabetes
European Journal of Internal Medicine, 2004
Background: In this study, we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 (BIAsp30) with that of biphasic human insulin 30 (BHI30) over a period of 24 months in patients with type 2 diabetes. Methods: Patients with type 2 diabetes (n=125) were assigned to twice-daily BIAsp30 or BHI30 and participated in both a 3-month initial period and a 21-month extension of a randomized, controlled, multinational trial. Results: No significant difference was found in mean HbA 1c after 24 months [BIAsp30, 8.35F0.20%; BHI30 8.13F0.16%; adjusted mean difference (BIAsp30ÀBHI30) 0.03 (90% CI À0.29 to 0.34)%, P=0.89]. The proportion of patients experiencing major hypoglycaemia was also similar during the first year (BIAsp30, 5%; BHI30, 8%; P=0.72), but it was significantly lower with BIAsp30 than with BHI30 during the second year (BIAsp30, 0%; BHI30, 10%; P=0.04). The proportion experiencing minor hypoglycaemia was not significantly different. No significant difference was recorded in changes in nonspecific insulin antibody levels after 24 months (BIAsp30, 4.87F1.92%; BHI30; 1.00F1.66%; P=0.13). Body weight change was 0.05F0.81 kg in the BIAsp30 group and 2.00F0.69 kg in the BHI30 group ( P=0.07). Conclusions: Reduced major hypoglycaemia compared with BHI30 during the second year of treatment and comparable HbA 1c levels after 24 months appear to support the hypothesis that the improved pharmacokinetic profile of BIAsp30 may favourably affect the balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes. D