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PubMed1999

Insulin aspart.

Insulin aspart is a recombinant analogue of human insulin. Following subcutaneous insulin injection (0.15 to 0.2 U/kg), significantly higher serum insulin concentrations are achieved in a shorter time with insulin aspart than with human insulin. The subsequent decline in serum insulin concentrations is also more rapid with insulin aspart. In healthy individuals undergoing euglycaemic glucose clamp testing, glucose infusion rates were higher and reached maximum concentrations significantly earlier after insulin aspart than after human insulin. Interindividual variability in pharmacodynamic and pharmacokinetic parameters with insulin aspart was generally less than that with human insulin, whereas the intraindividual variability in these parameters was similar after each insulin. In patients with type 1 diabetes postprandial glucose excursions were less pronounced with insulin aspart than human insulin. Daytime glucose control was better and minimum glucose levels during the night were not as low with insulin aspart as with human insulin. In diabetic patients treated with insulin aspart there was generally a lower frequency of hypoglycaemic events than in patients treated with human insulin.

Clinical Trials as Topic↗

PubMed2001

Clinical pharmacokinetics and pharmacodynamics of insulin aspart.

Insulin aspart is a novel rapid-acting insulin analogue with improved subcutaneous absorption properties when compared with soluble human insulin. Pharmacokinetic studies show an absorption profile with a time to reach peak concentration (t(max)) about half that of human insulin, a peak plasma drug concentration (Cmax) approximately twice as high and shorter residence time. The potency and bioavailability of insulin aspart are similar to those of human insulin. The pharmacokinetics of insulin aspart have been studied in healthy Caucasian and Asian-Japanese volunteers, in patients with type 1 and 2 diabetes mellitus, and in children with diabetes, with both pre- and postprandial administration and during continuous subcutaneous insulin infusion (CSII). The pharmacokinetic profile was similar to that of another rapid-acting insulin analogue, insulin lispro, on the basis of published information for that agent. Pharmacodynamic studies show a smaller excursion of postprandial glucose with insulin aspart injected subcutaneously just before the meal compared with soluble human insulin injected 30 minutes before the meal in patients with type 1 diabetes mellitus, and an equivalent control in patients with type 2 diabetes displaying residual insulin production. In a treatment study, glucose excursions evaluated from 24-hour glucose profiles showed less variability with insulin aspart compared with human insulin. Adverse events, including hypoglycaemia-induced ventricular repolarisation and hypoglycaemic threshold and awareness, did not differ between insulin aspart and human insulin. The available data suggest that subcutaneous injections of insulin aspart just before meals better mimic the endogenous insulin profile in blood compared with human insulin, resulting in improved glucose control in a meal-related insulin regimen. This review summarises the clinical pharmacokinetics and pharmacodynamics of insulin aspart in relation to human insulin and insulin lispro.

Adult↗

PubMed2002

A direct comparison of insulin aspart and insulin lispro in patients with type 1 diabetes.

OBJECTIVE: Both rapid-acting insulin analogs, insulin aspart and lispro, attenuate prandial glucose excursion compared with human soluble insulin. This trial was performed to study the pharmacokinetic and pharmacodynamic profiles of insulin aspart and insulin lispro in type 1 diabetic patients in a direct comparison and to investigate whether the administration of one analog results in favorable effects on prandial blood glucose control. RESEARCH DESIGN AND METHODS: A total of 24 type 1 diabetic patients (age 36 +/- 8 years, 16 men and 8 women, BMI 24.3 +/- 2.6 kg/m(2), diabetes duration 17 +/- 11 years, HbA(1c) 7.9 +/- 0.8%) on intensified insulin therapy were recruited into a single-center, randomized, double-blind, two-period, cross-over, glucose clamp trial. The subjects were given an individual need-derived dose of prandial insulin lispro or aspart immediately before a standard mixed meal. RESULTS: With respect to blood glucose excursions from time 0 to 6 h (Exc(glu(0-6 h))) and from time 0 to 4 h (Exc(glu(0-4 h))), the pharmacodynamic effect of insulin aspart and insulin lispro can be declared equivalent. This was supported by comparison with maximum postprandial blood glucose excursions (C(max(glu))) (estimated ratio aspart/lispro ANOVA [90% CI]: 0.95 [0.80-1.13], 0.97 [0.82-1.17], and 1.01 [0.95-1.07] for Exc(glu(0-6 h)), Exc(glu(0-4 h)), and C(max(glu)), respectively). For pharmacokinetic end points (maximum postprandial insulin excursions and area under the curve for insulin from time 0 to 6 h and from time 0 to 4 h), equivalence was indicated. No difference concerning absorption or elimination for time to maximal insulin concentration, time to half-maximum insulin concentration, and time to decrease to 50% of maximum insulin concentration was observed. CONCLUSIONS: These data suggest that in type 1 diabetic patients, both insulin analogs are equally effective for control of postprandial blood glucose excursions.

Adult↗

PubMed2006

Comparison of the pharmacokinetics and pharmacodynamics of biphasic insulin aspart and insulin glargine in people with type 2 diabetes.

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/m2 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.

Aged↗

PubMed2002

Immune responses to insulin aspart and biphasic insulin aspart in people with type 1 and type 2 diabetes.

OBJECTIVE: The antibody responses to a novel rapid-acting insulin analog, insulin aspart (IAsp), and their potential clinical correlates were studied with a specifically developed method in 2,420 people with diabetes treated for up to 1 year with preprandial subcutaneous injections of IAsp. RESEARCH DESIGN AND METHODS: Circulating insulin antibodies were analyzed by radioimmunoassay with (125)I insulin or IAsp tracers and polyethylene glycol precipitation. Four multinational, open, parallel group studies were conducted in Europe and North America, with a total of 1,534 people with diabetes exposed to IAsp and 886 people exposed to human insulin (HI) as meal-related insulin for 6-12 months. RESULTS: Insulin antibodies specific to HI or IAsp were absent in a majority of patients throughout the 6- to 12-month study periods. A majority of the patients (64-68%) had antibodies cross-reacting between HI and IAsp when entering the studies, with baseline levels (means +/- SD of percent bound/total) of 16.6 +/- 16.3% in study 1 and 10.3 +/- 14.0% in study 4. In all four studies, cross-reactive antibodies increased in patients exposed to IAsp, with a maximum at 3 months, and thereafter there was a decline toward baseline levels at 9-12 months (levels at 3 and 12 months: 22.3 +/- 19.7 and 16.8 +/- 16.5% in study 1 and 21.5 +/- 21.9 and 16.9 +/- 17.4% in study 4). Antibody levels showed similar changes in people with type 1 and type 2 diabetes, and there was no consistent relationship between antibody formation and glycemic control or between antibody formation and safety in terms of adverse events. CONCLUSIONS: Treatment with IAsp is associated with an increase in cross-reactive insulin antibodies, with a subsequent fall toward baseline values, without any indication of clinical relevance because no effect on efficacy or safety could be identified.

Adult↗

PubMed2004

A direct efficacy and safety comparison of insulin aspart, human soluble insulin, and human premix insulin (70/30) in patients with type 2 diabetes.

OBJECTIVE: Because there are limited data on the comparison of insulin aspart and mixed insulin in type 2 diabetes, this trial was performed to compare the efficacy and safety of preprandial insulin aspart with human soluble insulin (HI) and human premix (70% NPH/30% regular) insulin (MIX). RESEARCH DESIGN AND METHODS: A total of 231 type 2 diabetic patients were randomized to insulin aspart (n = 75), HI (n = 80), or MIX (n = 76) for 3 months. Insulin aspart and HI were administered with or without bedtime NPH insulin. A total of 204 patients completed the trial according to protocol. HbA1c, 7-point blood glucose, insulin dosage, and hypoglycemic episodes were recorded. The primary end point was "change of HbA1c" from baseline to last visit. Analysis for equivalence was performed by t tests with three subtests. RESULTS: HbA1c decreased 0.91 +/- 1.00 for insulin aspart, 0.73 +/- 0.87 for HI, and 0.65 +/- 1.10 for MIX with the following confidence intervals: insulin aspart HI (-0.21 to 0.57, P = 0.025), insulin aspart MIX (-0.17 to 0.69, P = 0.092), and HI-MIX (-0.33 to 0.48, P = 0.006). Postprandial blood glucose decreased in the insulin aspart group: 0.44 mmol/l to >1.67 mmol/l compared with HI and 1.1 mmol/l to >1.67 mmol/l compared with MIX. Preprandial insulin doses were similar in the insulin aspart and HI groups (10-14.5 U). Hypoglycemic events per month were 0.56 HI, 0.40 insulin aspart, and 0.19 MIX. CONCLUSIONS: Statistically, insulin aspart was not equivalent to another treatment in terms of HbA1c reduction. Insulin aspart treatment resulted in improved HbA1c and postprandial blood glucose. The application of insulin aspart was safe and well tolerated.

Blood Glucose↗

PubMed2000

Insulin aspart vs. human insulin in the management of long-term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trial.

AIMS: To compare the efficacy of insulin aspart, a rapid-acting insulin analogue, with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus. METHODS: Prospective, multi-centre, randomized, open-labelled, parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1,070 adult subjects with Type 1 diabetes. Study patients were randomized 2:1 to insulin aspart or unmodified human insulin before main meals, with NPH-insulin as basal insulin. Main outcome measures were blood glucose control as assessed by HbA1c, eight-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia, and adverse events. RESULTS: After 6 months, insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 (95% confidence interval 0.03-0.22) %Hb, P < 0.02. Eight-point blood glucose profiles showed lower post-prandial glucose levels (mean baseline-adjusted -0.6 to -1.2 mmol/l, P < 0.01) after all main meals, but higher pre-prandial glucose levels before breakfast and dinner (0.7-0.8 mmol/l, P < 0.01) with insulin aspart. Satisfaction with treatment was significantly better in patients treated with insulin aspart (WHO Diabetes Treatment Satisfaction Questionnaire (DTSQ) baseline-adjusted difference 2.3 (1.2-3.3) points, P < 0.001). The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 (0.59-1.18, NS). Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart (1.3 vs. 3.4% of patients, P < 0.05), as were late post-prandial (4-6 h) events (1.8 vs. 5.0% of patients, P < 0.005). CONCLUSIONS: These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control, hypoglycaemia, and quality of life, in people with Type 1 diabetes mellitus.

Adult↗

PubMed2002

Insulin aspart (AspB28 human insulin) derivatives formed in pharmaceutical solutions.

PURPOSE: To isolate and identify the main insulin aspart (AspB28 human insulin) derivatives formed in pharmaceuticals (pH 7.4 at 5 degrees C), to estimate rates of formation, and to determine their biologic potencies. METHODS: Insulin aspart derivatives have been isolated by reversed-phase high-performance liquid chromatography (RP-HPLC), and identified by RP-HPLC, peptide mapping, amino acid analysis, mass spectrometry. and N-terminal amino acid sequence analysis. RESULTS: The main derivatives formed were isoAspB28, isoAspB3, AspB3, and desPheB1-N-oxalyl-ValB2 insulin aspart. At 5 degrees C, the rate constants were 0.00028/month for isoAspB28 and isoAspB3, 0.00024/month for AspB3, and 0.00013/month for desPheB1-N-oxalyl-ValB2 derivatives of insulin aspart. Unexpectedly, the rate of isomerization of B28 was high compared to the rate of B3 deamidation at both 5 degrees C and 45 degrees C. The N-terminal and especially the C-terminal of the B-chain are highly flexible, which may explain the high rate of isoAspB28 formation and that deamidation of AsnB3 occurs. All the derivatives had full in vivo biologic potencies. CONCLUSION: Except for isoAspB28 insulin aspart, the main derivatives formed in pharmaceuticals of insulin aspart and human insulin at pH 7.4 are similar. They are all fully active in vivo. In proteins, flexibility of the polypeptide chain seems more important than sequence in the formation of succinimides.

Amino Acid Sequence↗

PubMed2004

Treatment of diabetic ketoacidosis with subcutaneous insulin aspart.

OBJECTIVE: In this prospective, randomized, open trial, we compared the efficacy and safety of aspart insulin given subcutaneously at different time intervals to a standard low-dose intravenous (IV) infusion protocol of regular insulin in patients with uncomplicated diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS: A total of 45 consecutive patients admitted with DKA were randomly assigned to receive subcutaneous (SC) aspart insulin every hour (SC-1h, n = 15) or every 2 h (SC-2h, n = 15) or to receive IV infusion of regular insulin (n = 15). Response to medical therapy was evaluated by assessing the duration of treatment until resolution of hyperglycemia and ketoacidosis. Additional end points included total length of hospitalization, amount of insulin administration until resolution of hyperglycemia and ketoacidosis, and number of hypoglycemic events. RESULTS: Admission biochemical parameters in patients treated with SC-1h (glucose: 44 +/- 21 mmol/l [means +/- SD], bicarbonate: 7.1 +/- 3 mmol/l, pH: 7.14 +/- 0.09) were similar to those treated with SC-2h (glucose: 42 +/- 21 mmol/l, bicarbonate: 7.6 +/- 4 mmol/l, pH: 7.15 +/- 0.12) and IV regular insulin (glucose: 40 +/- 13 mmol/l, bicarbonate 7.1 +/- 4 mmol/l, pH: 7.11 +/- 0.17). There were no statistical differences in the mean duration of treatment until correction of hyperglycemia (6.9 +/- 4, 6.1 +/- 4, and 7.1 +/- 5 h) or until resolution of ketoacidosis (10 +/- 3, 10.7 +/- 3, and 11 +/- 3 h) among patients treated with SC-1h and SC-2h or with IV insulin, respectively (NS). There was no mortality and no differences in the length of hospital stay, total amount of insulin administration until resolution of hyperglycemia or ketoacidosis, or the number of hypoglycemic events among treatment groups. CONCLUSIONS: Our results indicate that the use of subcutaneous insulin aspart every 1 or 2 h represents a safe and effective alternative to the use of intravenous regular insulin in the management of patients with uncomplicated DKA.

Adult↗

PubMed2007

Insulin therapy in type 2 diabetes patients failing oral agents: cost-effectiveness of biphasic insulin aspart 70/30 vs. insulin glargine in the US.

OBJECTIVES: To project the long-term clinical and economic outcomes of treatment with biphasic insulin aspart 30 (BIAsp 70/30, 30% soluble and 70% protaminated insulin aspart) vs. insulin glargine in insulin-naïve type 2 diabetes patients failing to achieve glycemic control with oral antidiabetic agents alone (OADs). METHODS: Baseline patient characteristics and treatment effect data from the recent 'INITIATE' clinical trial served as input to a peer-reviewed, validated Markov/Monte-Carlo simulation model. INITIATE demonstrated improvements in HbA1c favouring BIAsp 70/30 vs. glargine (-0.43%; p < 0.005) and greater efficacy in reaching glycaemic targets among patients poorly controlled on OAD therapy. Effects on life expectancy (LE), quality-adjusted life expectancy (QALE), cumulative incidence of diabetes-related complications and direct medical costs (2004 USD) were projected over 35 years. Clinical outcomes and costs were discounted at a rate of 3.0% per annum. Sensitivity analyses were performed. RESULTS: Improvements in glycaemic control were projected to lead to gains in LE (0.19 +/- 0.24 years) and QALE (0.19 +/- 0.17 years) favouring BIAsp 70/30 vs. glargine. Treatment with BIAsp 70/30 was also associated with reductions in the cumulative incidences of diabetes-related complications, notably in renal and retinal conditions. The incremental cost-effectiveness ratio was $46 533 per quality-adjusted life year gained with BIAsp 70/30 vs. glargine (for patients with baseline HbA1c >/= 8.5%, it was $34 916). Total lifetime costs were compared to efficacy rates in both arms as a ratio, which revealed that the lifetime cost per patient treated successfully to target HbA1c levels of <7.0% and </= 6.5% were $80 523 and $93 242 lower with BIAsp 70/30 than with glargine, respectively. CONCLUSIONS: Long-term treatment with BIAsp 70/30 was projected to be cost-effective for patients with type 2 diabetes insufficiently controlled on OADs alone compared to glargine. Treatment with BIAsp 70/30 was estimated to represent an appropriate investment of healthcare dollars in the management of type 2 diabetes.

Administration, Oral↗

PubMed2005

Long-term clinical and cost outcomes of treatment with biphasic insulin aspart 30/70 versus insulin glargine in insulin naïve type 2 diabetes patients: cost-effectiveness analysis in the UK setting.

OBJECTIVES: To evaluate the long-term clinical and cost outcomes associated with biphasic insulin aspart 30/70 (BIAsp 30/70, premixed 30% soluble and 70% protaminated insulin aspart in one injection) compared to insulin glargine treatment in insulin-naïve type 2 diabetes patients failing oral antidiabetic agents in the UK, based on findings recently reported from the INITIATE clinical trial. METHODS: The CORE Diabetes Model, a published, peer-reviewed and validated model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy, cumulative incidence of complications and direct medical costs over patient lifetimes. The model simulates the range of diabetic complications and disease progression within a series of sub-models (cardiovascular disease, neuropathy, renal and eye disease) based on published data. Baseline cohort characteristics (54.5% male, mean age 52.45 years, mean diabetes duration 9 years, mean HbA(1c) 9.77%) and treatment effects were based on INITIATE. Costs were derived from published UK sources. The analysis was run over a 35-year time horizon (patient lifetime) from a third party payer perspective. Costs and clinical benefits were discounted at 3.5% per annum. Sensitivity analyses were performed. RESULTS: BIAsp 30/70 was associated with projected improvements in discounted life expectancy (0.19 +/- 0.20 years) and quality-adjusted life expectancy (0.19 +/- 0.14 quality-adjusted life years [QALYs]), as well as a reduced incidence of retinopathy and nephropathy complications, versus glargine. Total lifetime direct costs were 1319 pounds higher with BIAsp 30/70 than with glargine leading to an incremental cost-effectiveness ratio of 6951 pounds per QALY gained. CONCLUSIONS: This study is the first to address the long-term health economic implications of treating type 2 diabetes patients failing oral anti-diabetics with a biphasic insulin mix versus long-acting insulin. Our projections indicate that improved HbA1c levels with BIAsp 30/70 treatment are associated with improvements in life expectancy and quality-adjusted life expectancy, and that BIAsp 30/70 represents excellent value for money compared to insulin glargine in the UK.

Adult↗

PubMed2001

Glycaemic control in type 1 diabetic patients using optimised insulin aspart or human insulin in a randomised multinational study.

Insulin aspart (IAsp), is a rapid-acting analogue of human insulin (HI), for use in the meal related treatment of diabetes mellitus. The degree of glycaemic control achieved by IAsp in comparison with HI after algorithm-driven dose optimisation was tested over 3 months. The prospective, multicentre, randomised, open-label study with parallel groups was performed in 48 centres in 11 countries and included 423 basal-bolus treated patients with Type 1 diabetes. Main outcome measures were blood glucose control assessed by HbA1c, nine-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia and adverse events. An algorithm-driven increase occurred in the dose and number of daily injections of basal insulin, particularly in the IAsp group. After 12 weeks of treatment, HbA1c was significantly lower in IAsp compared to HI treated subjects by 0.17 (95% CI 0.30-0.04) (P<0.05). Comparison of the blood glucose profiles showed lower blood glucose levels with IAsp after breakfast (mean 8.4 vs 10.1 mmol/l; P<0.0001) and dinner (8.2 vs 9.3 mmol/l; P<0.01). There were no differences between treatments in the incidence of hypoglycaemic episodes or in the adverse event profiles. The WHO Diabetes Treatment Satisfaction Questionnaire score for perceived hyperglycaemia was lower with Iasp (P=0.005), and patients found the insulin aspart treatment more flexible (P=0.022). The current study underlines the need for optimising the basal insulin regimen in order to take full advantage of the pharmacodynamics of IAsp.

Adult↗

PubMed1999

Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects.

OBJECTIVE: To study the pharmacokinetic and pharmacodynamic profile of insulin aspart (a new fast-acting human insulin analog) after subcutaneous administration in the deltoid, abdominal, and thigh sites and to compare this profile with regular human insulin (Novolin; Novo Nordisk A/S, Copenhagen). RESEARCH DESIGN AND METHODS: A total of 20 healthy subjects were studied in a single-center six-period double-blind randomized crossover trial with 6 study days and a washout period of 1 week between each single daily dose of the trial drug. Subjects were randomized to receive a single dose of 0.2 U/kg of insulin aspart or regular insulin on each of the 6 study days in three different sites (the deltoid, the abdomen, and the thigh) during a 10-h euglycemic clamp (two drugs and three injection sites). Pharmacokinetic and pharmacodynamic measurements were derived from blood sample measurements of glucose, insulin, and C-peptide during these clamps. RESULTS: The pharmacodynamic data from the euglycemic clamp study showed that, regardless of injection site, the maximal glucose infusion rate (GIR Cmax) was greater and occurred at an earlier time (GIR Tmax) after administration of insulin aspart than regular insulin (GIR Cmax: abdomen 813 vs. 708, deltoid 861 vs. 736, and thigh 857 vs. 720 g/min, P < 0.05 for all; GIR Tmax: abdomen 94 vs. 173, deltoid 111 vs. 192, and thigh 145 vs. 193 g/min, P < 0.05 for all). Pharmacokinetic parameters were also consistent with faster absorption and higher peak insulin concentrations after insulin aspart administration. From all sites, the peak insulin concentration (Cmax) was higher and occurred earlier (Tmax) after administration of insulin aspart than of regular insulin (Cmax: abdomen 501 vs. 260, deltoid 506 vs. 252, thigh 422 vs. 220 pmol/l, P < 0.001 for all sites; Tmax: abdomen 52 vs. 109, deltoid 54 vs. 98, and thigh 60 vs. 107 min, P < 0.01 for all sites). The absorption and glucose-lowering action of insulin aspart did not differ between sites (similar GIR Cmax, Tmax, and area under the curve parameters). However, the duration of the glucose-lowering effect was up to 34 min shorter (P < 0.01) for the abdomen injections than for the deltoid or thigh injections (lower time of 50% glucose disposal). In addition, the amount of glucose infused was significantly lower by 10-14% in the abdomen than in other sites. CONCLUSIONS: Subcutaneous administration of insulin aspart causes a more rapid and intense maximal effect compared with regular insulin during euglycemic clamp studies in nondiabetic subjects. Abdominal administration of insulin aspart has a shorter duration of glucose-lowering effect compared with administration in the deltoid or thigh.

Absorption↗

PubMedDate not supplied

Symptomatic and counterregulatory hormonal responses to acute hypoglycaemia induced by insulin aspart and soluble human insulin in Type 1 diabetes.

BACKGROUND: The aim of this study was to assess hypoglycaemia awareness with the insulin analogue, insulin aspart. The counterregulatory hormonal and symptomatic responses to hypoglycaemia induced by insulin aspart were compared with soluble human insulin in a double-blind, randomised, two-period crossover trial in patients with Type 1 diabetes. The primary objective was to compare the blood glucose threshold for autonomic activation during hypoglycaemia induced by insulin aspart and soluble human insulin. Secondary objectives were to compare the counterregulatory, symptomatic and physiological responses to hypoglycaemia. METHODS: 20 patients were screened, 17 were randomised and 16 completed the study. Acute hypoglycaemia was induced by intravenous infusion of insulin aspart or soluble human insulin (100 U ml(-1) at a rate of 2 mU kg(-1) min(-1)). RESULTS: No statistical difference between insulin aspart and soluble human insulin was shown for the primary blood glucose endpoint; mean arterialised blood glucose concentrations (+/-SD) at the onset of autonomic activation were 1. 88+/-0.39 mmol L(-1) for insulin aspart and 1.89+/-0.43 mmol L(-1) for soluble human insulin (not significant). No statistical differences were observed between the two insulins for the secondary endpoints: counterregulatory hormonal responses, autonomic responses, hypoglycaemia symptom scores, cognitive function and blood glucose responses. No serious adverse events were reported during the study. CONCLUSIONS: Insulin aspart and soluble human insulin elicit the same counterregulatory and symptomatic responses to acute hypoglycaemia in patients with Type 1 diabetes.

Adolescent↗

PubMed2004

Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy, using either the soluble long-acting basal insulin analogue, insulin detemir, in combination with the rapid-acting analogue, insulin aspart, or NPH insulin in combination with mealtime regular human insulin. METHODS: In this 18-week, 1:1 randomised, open-labelled, parallel trial, 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively. RESULTS: Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin (HbA1c: 7.88% vs 8.11%; mean difference: -0.22% point [95% CI: -0.34 to -0.10]; p<0.001). Self-measured 8-point plasma glucose profiles differed between the groups (p<0.001), with lower postprandial plasma glucose levels in the insulin detemir/insulin aspart group. Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (SD: 2.88 vs 3.12 mmol/l; p<0.001). Risk of overall and nocturnal hypoglycaemia (23.00-06.00 hours) was, respectively, 21% (p=0.036) and 55% (p<0.001) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group. Body weight (adjusted for baseline and change in HbA1c) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (p<0.001). CONCLUSIONS/INTERPRETATION: Basal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin. The low variability and more physiological action profiles generated with these insulin analogues resulted in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase.

Adult↗

PubMed2006

Therapeutic efficacy of mitiglinide combined with once daily insulin glargine after switching from multiple daily insulin regimen of aspart insulin and glargine in patients with type 2 diabetes mellitus.

Mitiglinide is novel class of rapid-acting insulin secretagogues, which have been widely used alone or in combination with other oral hypoglycemic drugs to improve postprandial hyperglycemia in early type 2 diabetes. While mitiglinide enhances postprandial requirement of insulin, the efficacy of mitiglinide combined with insulin has yet to be established. We investigated the efficacy of mitiglinide combined with insulin glargine, the first soluble insulin analog that has a flat and prolonged effect. After control with the intensive regimen (daily aspart insulin and glargine), 30 inpatients with type 2 diabetes were switched to premeal mitiglinide combined with once daily insulin glargine (mitiglinide regimen), and daily profiles of blood glucose level were compared under each regimen. Fifteen patients showed similar control of hyperglycemia with mitiglinide regimen and intensive insulin regimen, assessed by M value (<32), while the remaining 15 showed worsening under the mitiglinide regimen. The patients who were well controlled with mitiglinide regimen were significantly younger (51.9 +/- 16.0 years, p<0.005) and heavier (body mass index: 25.7 +/- 3.3 kg/m(2), p<0.05) than those who were not (67.9 +/- 8.7 and 23.0 +/- 3.1, respectively). Moreover, insulin doses of aspart per body weight were significantly fewer in effective group than in ineffective group. Duration of diabetes was shorter in the effective group, albeit insignificantly. Previous treatment before starting intensive insulin regimen, such as insulin and sulfonylurea, was not different between the two groups. Our results suggest that mitiglinide plus insulin glargine combination therapy is useful for lowering both fasting and postprandial hyperglycemia in a subpopulation of type 2 diabetes. The long-term effects of such treatment need to be established in future studies.

Adult↗

PubMed2004

Randomized, multinational, open-label, 2-period, crossover comparison of biphasic insulin aspart 30 and biphasic insulin lispro 25 and pen devices in adult patients with type 2 diabetes mellitus.

OBJECTIVE: The goal of this study was to compare the efficacy and safety profiles of biphasic insulin aspart 30 (30% soluble insulin aspart and 70% protaminated insulin aspart [BIAsp 30]) and biphasic insulin lispro 25 (25% soluble insulin lispro and 75% neutral protamine lispro [Mix25]) used in a BID injection regimen in patients with type 2 diabetes mellitus (DM). Also assessed was patients' preference for pen device--the NovoMix 30 FlexPen /NovoLog Mix 70/30 FlexPen (FlexPen) versus the Humalog Mix25 Pen/Humalog Mix75/25 Pen (Humalog Pen). METHODS: Patients with type 2 DM receiving current insulin treatment were randomized to a multinational, multicenter, open-label, 2-period, crossover comparison of BIAsp 30 and Mix25. Efficacy (by analyses of variance) and safety profiles were assessed after 12 weeks of treatment. Patients' preference for pen device was assessed by questionnaires. RESULTS: A total of 137 patients were randomized to treatment; 4 were withdrawn during the 2-week run-in treatment with biphasic human insulin 30. The mean (SD) characteristics of the remaining 133 patients (79 men, 54 women) were as follows: age, 62.3 (9.2) years; body mass index, 28.1 (3.9) kg/m(2); and glycosylated hemoglobin (HbA(1c)), 8.5% (1.1). Glycemic control was assessed by the measurement of HbA(1c) after 12 weeks of treatment. Treatment with BIAsp 30 was noninferior to treatment with Mix25 (upper limit of 90% CI for estimated difference [BIAsp 30 - Mix25] was <0.4%). Self-monitored blood glucose levels were comparable (P = NS). Adverse-event profiles were similar between treatments, as was the incidence of hypoglycemic episodes (0.69 episode/mo with BIAsp 30 and 0.62 episode/mo with Mix25, P = 0.292). For all device features assessed, the FlexPen consistently received higher scores (all P < 0.005). A total of 9.0% of patients experienced problems with the FlexPen, compared with 32.4% with the Humalog Pen (P < 0.001). Furthermore, 74.6% preferred to continue using the FlexPen, whereas 14.3% preferred the Humalog Pen (P < 0.001). CONCLUSIONS: In this study, glycemic control with BIAsp 30 and Mix25 was found to be comparable in these patients with type 2 DM. Safety profiles were similar for both regimens. Patients preferred and experienced fewer problems with the FlexPen than the Humalog Pen.

Biphasic Insulins↗

PubMed2003

Comparison of an insulin analog, insulin aspart, and regular human insulin with no insulin in gestational diabetes mellitus.

OBJECTIVE: To assess the short-term efficacy of insulin aspart in comparison with regular human insulin in women with gestational diabetes mellitus (GDM) during standardized meal tests. RESEARCH DESIGN AND METHODS: The study included 15 women with GDM who had inadequate diabetes control with diet alone. On 3 consecutive days, breakfast meal tests were performed-the first with no exogenous insulin and the other two after the injection of either regular insulin or insulin aspart. RESULTS: The peak insulin concentration was higher and the peak glucose and C-peptide concentrations were lower with both insulin preparations than with no exogenous insulin. Glucose areas under the curve above baseline were significantly lower with insulin aspart (180-min area, 7.1 mg. h. dl(-1); P = 0.018), but not with regular insulin (30.2 mg. h. dl(-1); P = 0.997), than with no insulin (29.4 mg. h. dl(-1)). CONCLUSIONS: This study demonstrates that effective postprandial glycemic control in women with GDM who required insulin was brought about by insulin aspart through higher insulin peak and lower demand on endogenous insulin secretion.

Adult↗