Formulation Of Insulin Aspart Research Articles

Effectiveness of Faster Aspart versus Insulin Aspart in Children with Type 1 Diabetes: A Meta-Analysis.

Intensive insulin regimens are recommended to achieve glycemic goals in children and adolescents with type 1 diabetes. Fast-acting insulin aspart (faster aspart) is a new formulation of insulin aspart (IAsp) in which L-arginine and niacinamide are added to assure formulation stability, early absorption, and ultra-fast action. This meta-analysis compares faster aspart with IAsp for blood sugar control in children with type 1 diabetes. This study suggested treating diabetes with insulin, especially in children with type 1 diabetes. PubMed, MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar were searched from 2000 to 2023 without language restrictions. Blood glucose monitoring, HbA1c, care model, insulin aspart, IAsp, faster aspart, type 1 diabetes, and pediatrics are Mesh keywords. Cochrane Q statistics and index tested heterogeneity. To account for heterogeneity, Q=145.99 (P-value < 0.001) and =97.26%, and the random-effect model was used to aggregate primary study results. The meta-analysis of randomized-controlled trials was conducted in accordance with PRISMA standards. The overall estimate measure i.e. mean difference was found to be 5.44 [0.45, 10.44] and 7.71 [7.16, 8.26] which indicate significant reduction in the HbA1C level in the fast acting insulin aspart group as compared to the IAsp in T1D. However, the mean difference with respect to BMI was found to be -0.06 [-0.60, 0.48] which indicate non-significant reduction. Faster aspart had faster onset and more early exposure than IAsp in children and adolescents with greater and more variable anti-insulin antibody levels than adults did. Hence fast-acting insulin aspart may provide better glucose control than IAsp in T1D.

Faster Insulin Aspart for Continuous Subcutaneous Insulin Infusion: Is It Worth It?

IntroductionFaster insulin aspart (fASP) is the new formulation of insulin aspart (ASP) with a left-shifted pharmacokinetic profile, allowing better control of early postprandial hyperglycemia and a reduction in the risk of late post-meal hypoglycemia. However, it can be associated with more frequent infusion set changes. The purpose of this study is to evaluate efficacy and safety one, three, and six months after starting fASP in continuous subcutaneous insulin infusion (CSII) systems.MethodsThis is a retrospective study that included adults with type 1 diabetes mellitus, users of CSII ≥3 months, who started fASP. Exclusion criteria included less than one month of follow-up after the intervention, concomitant initiation of pharmacological therapy, pre-conception period, and non-use of continuous glucose monitoring.ResultsA total of 77 individuals were included, of which 52 (67.5%) were female, aged 39.87 ± 13.10 years, with a mean time under CSII of 7.30 ± 3.58 years and a median follow-up time after transition to fASP of six months. There was a trend to a global glycemic control improvement at six months after starting fASP: numeric increase in time in range (56.40 ± 12.62% vs 60.15 ± 13.53%, p=0.148), reduction in time above range (37.76 ± 13.05% vs 34.67 ± 14.94%, p=0.557), time below range (6.00 (5.00)% vs 4.50 (5.25)%, p=0.122), and mean glucose (174.29 ± 25.14 mg/dL vs 167.00 ± 25.30 mg/dL, p=0.207). There was a reduction in body mass index (BMI) at six months after switching to fASP (25.08 (4.59) kg/m2 vs 24.45 (3.05) kg/m2, p=0.010), despite the absence of a significant variation in total daily insulin. Adverse event and discontinuation rates were 7.8% and 6.5%, respectively, with no documented episodes of diabetic ketoacidosis or severe hypoglycemia.ConclusionsfASP proved to be a safe and effective therapeutic option in CSII systems associated with a significant BMI reduction, aspects that might justify its preference.

Comparative efficacy and safety of two insulin aspart formulations (Rapilin and NovoRapid) when combined with metformin, for patients with diabetes mellitus: a multicenter, randomized, open-label, controlled clinical trial

Objective This phase 3 confirmatory diabetes mellitus treatment study compared the safety and efficacy of Rapilin and NovoRapid insulin asparts in combination with metformin. Methods This 24-week, open-label, randomized, active-controlled, noninferiority phase 3 confirmatory study conducted across centers in China aimed to enroll patients with type 2 diabetes mellitus and blood sugar glucose inadequately controlled by oral antidiabetic drugs. Randomized patients received subcutaneous mealtime Rapilin or NovoRapid (3:1) injections, with metformin. The primary objectives were to demonstrate noninferiority (margin of 0.4%) in HbA1c change from baseline and compare safety profiles of Rapilin versus NovoRapid after 24 weeks. Secondary outcomes included 2-h postprandial plasma glucose (PPG), fasting plasma glucose (FPG), and patients achieving HbA1c <7.0% and ≤6.5%. Results 590 patients with type 2 diabetes mellitus were randomized to Rapilin (n = 441) and NovoRapid (n = 149) groups. After 24 weeks, the mean HbA1c change from baseline was −2.20% (Rapilin) and −2.32% (NovoRapid); the estimated treatment difference based on least-square means was 0.04% (95% CI: −0.17, 0.26), meeting the noninferiority criteria for Rapilin versus NovoRapid. Comparable improvements were reported for mean 2-hour PPG (6.14 and 6.29 mmol/L), FPG (2.02 and 1.70 mmol/L), and patients with HbA1c <7.0% (52.6% and 51.0%) and ≤6.5% (34.2% and 30.9%), in the Rapilin and NovoRapid groups, respectively, with no significant safety or immunogenicity outcome differences. Conclusions Rapilin demonstrated non-inferior glycemic control, and matching safety and immunogenicity to NovoRapid in patients with type 2 diabetes mellitus also receiving metformin over 24 weeks. Trial registration ChiCTR20003129041

Modeling of Pharmacokinetic Profiles of Insulin Aspart and Biphasic Insulin Aspart 30/70.

This study includes modeling and simulation of insulin aspart pharmacokinetics (PK). The authors used PK data of biosimilar insulins-insulin aspart and biphasic insulin aspart 30/70-to develop a predictive population PK model for the insulins. The model was built via Monolix software, taking into account the weight-based dosing and the dose and body-weight effects on the parameters. The model-based simulations were performed using the R package mlxR for various administered doses and various ratios of insulin aspart forms for a better understanding of the insulin behavior. The optimal model was a 1-compartment model with a combination of zero- and first-order absorptions, with absorption lag for the soluble form of insulin aspart and first-order absorption for the insulin aspart protamine suspension. The assumption of identical behavior of 2 insulins at the distribution and elimination phases was made. The developed PK model was fitted successfully to the experimental data, and all fitted parameters displayed a moderate coefficient of variation. The PK model allows us to predict PK profiles for various doses and formulations of insulin aspart and can be used to improve the accuracy, safety, and ethics of novel clinical trials of insulin.

Can Faster Aspart Be Used to Optimize Glycemic Control With Insulin Pump Therapy? From Expectations to Lessons Learned After a Year of Use in the United States.

Fast-acting insulin aspart (faster aspart) is an ultra-rapid-acting formulation of insulin aspart developed to more closely match the prandial endogenous insulin profile, and its accelerated absorption kinetics are expected to provide clinical benefits for patients using insulin pump therapy. A head-to-head trial versus the original insulin aspart formulation in pump therapy did not demonstrate superiority of faster aspart in terms of A1C reduction, but pump settings were not optimized for the pharmacokinetic/pharmacodynamic profile of faster aspart. Nevertheless, meal test and continuous glucose monitoring data suggest that faster aspart is beneficial for postprandial glucose control, and a case study is presented illustrating excellent results using this insulin in pump therapy. Frequent blood glucose monitoring and appropriate patient education are vital for success.

Pharmacokinetics and Pharmacodynamics of Three Different Formulations of Insulin Aspart: A Randomized, Double-Blind, Crossover Study in Men With Type 1 Diabetes.

OBJECTIVETo investigate the pharmacokinetic and pharmacodynamic properties and safety of a novel formulation of insulin aspart (AT247) versus two currently marketed insulin aspart formulations (NovoRapid [IAsp] and Fiasp [faster IAsp]).RESEARCH DESIGN AND METHODSThis single-center, randomized, double-blind, three-period, crossover study was conducted in 19 men with type 1 diabetes, receiving single dosing of trial products (0.3 units/kg) in a random order on three visits. Pharmacokinetics and pharmacodynamics were assessed during a euglycemic clamp lasting up to 8 h.RESULTSOnset of insulin appearance was earlier for AT247 compared with IAsp (−12 min [95% CI −14; −8], P = 0.0004) and faster IAsp (−2 min [−5; −2], P = 0.0003). Onset of action was accelerated compared with IAsp (−23 min [−37; −15], P = 0.0004) and faster IAsp (−9 min [−11; −3], P = 0.0006). Within the first 60 min, a higher exposure was observed for AT247 compared with IAsp by the area under the curve (AUC) glucose infusion rate (GIR) from 0 to 60 min (AUCAsp0–60min: treatment ratio vs. IAsp 2.3 [1.9; 2.9] vs. faster IAsp 1.5 [1.3; 1.8]), which was underpinned by a greater early glucose-lowering effect (AUCGIR,0–60min: treatment ratio vs. IAsp 2.8 [2.0; 5.5] vs. faster IAsp 1.7 [1.3; 2.3]). Furthermore, an earlier offset of exposure was observed for AT247 compared with IAsp (−32 min [−58; −15], P = 0.0015) and faster IAsp (−27 min [−85; −15], P = 0.0017), while duration of the glucose-lowering effect, measured by time to late half-maximum effect, did not differ significantly.CONCLUSIONSAT247 exhibited an earlier insulin appearance, exposure, and offset, with corresponding enhanced early glucose-lowering effect compared with IAsp and faster IAsp. It therefore represents a promising candidate in the pursuit for second-generation prandial insulin analogs to improve postprandial glycemic control.

231-OR: Phase I Study Investigating the PD, PK, and Safety of AT247 in Comparison with Novorapid and Fiasp

Background: AT247, an ultra-rapid acting formulation of insulin aspart designed for faster absorption following s.c. injection, will lead to better postprandial glycaemic control and is key to the development of closed-loop pump systems. Method: Plasma glucose and serum insulin concentrations were measured in 19 adult male participants with T1DM following a single s.c. dose (0.3 U/Kg) of insulin in a randomised, double-blind, cross over euglycaemic clamp study. Results: Data presented as median; range. AT247 had a faster onset of glucose lowering effect than NovoRapid® and Fiasp® (onset of action: 17; 12-30 vs. 37; 20-88 vs. 23;16-50 mins). The early glucose lowering effect was greater for AT247 than NovoRapid® and Fiasp® (AUCGIR 0-60min: 212; 63-465 vs. 49; 0-303 vs. 91; 11-300 mg/kg; GIR=glucose infusion rate) (Fig 1A). Similarly, greater initial insulin exposure was seen for AT247 compared to NovoRapid® and Fiasp® (AUC Insulin 0-60min: 111; 48-205 vs. 41; 12-147 vs. 66; 25-188 mU*h/L). In addition, offset of exposure occurred earlier for AT247 than NovoRapid® and Fiasp® (time to late 50% Cmax Insulin: 173; 89-414 vs. 212; 106-389 vs. 221;106-441 mins). (Fig 1B). Comparisons are statistically significant with p&amp;lt;0.05. No safety signals were detected for AT247. Conclusion: AT247 has a superior (left-shifted) time-action and time-concentration profile as compared to both NovoRapid® and Fiasp®. Disclosure T.R. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S, Roche Diagnostics K.K. T. Augustin: None. C. Magnes: None. D.J. Gerring: None. J. Jezek: None. S.J. Howell: None. L. Zakrzewski: None. F.J. Lawrence: None. E. Svehlikova: None.

The association between anti-insulin aspart antibodies and the pharmacokinetic and pharmacodynamic characteristics of fast-acting insulin aspart in children and adolescents with type 1 diabetes.

BackgroundFast‐acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) ensuring ultrafast absorption and effect.AimTo compare the pharmacokinetics between faster aspart and IAsp, based on free or total IAsp measurement, and investigate the association between anti‐IAsp antibodies and faster aspart and IAsp pharmacological properties in children and adolescents with type 1 diabetes (T1D).MethodsIn a randomized, two‐period crossover trial, 12 children, 16 adolescents, and 15 adults (6‐11, 12‐17, and 18‐64 years) received 0.2 U/kg double‐blindsingle‐dose subcutaneous faster aspart or IAsp followed by a standardized liquid meal test.ResultsAcross age groups, the pharmacokinetic profile was left‐shifted including greater early exposure for faster aspart vs IAsp irrespective of free or total IAsp assay. Onset of appearance occurred 2.4 to 5.0 minutes (free) or 1.8 to 3.0 minutes (total) earlier for faster aspart vs IAsp (P < .05). Treatment ratios (faster aspart/IAsp) for 0 to 30 minutes IAsp exposure were 1.60 to 2.11 and 1.62 to 1.96, respectively (children, free: P = .062; otherwise P < .05). The ratio of free/total IAsp for overall exposure (AUCIAsp,0‐t) was negatively associated with anti‐IAsp antibody level across age. Pooling with a previous similar trial showed no clear association between anti‐IAsp antibodies and meal test 1‐ or 2‐hour postprandial glucose increment independent of age and insulin treatment (R 2 ≤ .070; P ≥ .17).ConclusionsIn children and adolescents with T1D, faster aspart provides ultrafast pharmacokinetics irrespective of free or total IAsp assay. Elevated anti‐IAsp antibodies are associated with higher total IAsp concentration, but do not impact faster aspart and IAsp glucose‐lowering effect.

Pharmacokinetics of Faster and Standard Insulin Aspart During Fully Closed-Loop Insulin Delivery in Type 2 Diabetes.

Background: Faster insulin aspart is a novel formulation of insulin aspart aiming to accelerate its subcutaneous absorption. The aim of this study was to compare pharmacokinetics of faster insulin aspart versus standard insulin aspart in adults with type 2 diabetes during closed-loop insulin delivery. Methods: We assessed the pharmacokinetics of faster and standard insulin aspart from data obtained in a randomized double-blind crossover study evaluating fully closed-loop insulin delivery in adults with type 2 diabetes (n = 13, age 59 ± 10 years, BMI 34.5 ± 9.1 kg/m2, HbA1c 7.7% ± 1.2% [60 ± 13 mmol/mol]). Blood samples were collected every 15-30 min for 10 h to determine plasma insulin aspart concentration using liquid chromatography mass spectrometry. Time to peak plasma concentration (Tmax) was calculated using a two-compartment model. Results:Tmax was 68.7 ± 21.6 min for faster aspart and 89.7 ± 31.8 min for aspart (mean paired difference faster aspart minus aspart -15.5 min, 95% CI [-31.6 to 0.6 min], P = 0.06). Metabolic clearance rate did not differ between the two insulins (P = 0.61). Insulin amount delivered during closed-loop with faster aspart positively correlated with Tmax (rS = 0.73, P = 0.01), whereas no statistically significant correlation was found with body mass index (BMI), weight or HbA1C (all P > 0.18). Conclusion: In conclusion, Tmax tended to be shorter for faster aspart versus aspart during fully automated closed-loop insulin delivery and positively correlated with the amount of insulin delivered.

Biosimilars and Novel Insulins.

Insulin therapy is the mainstay of treatment for type 1 diabetes and may be necessary in type 2 diabetes. Current insulin analogues present a more physiological profile, are effective, and with less risk of hypoglycemia, but they are expensive. Biosimilar insulins should offer the advantages of insulin analogues at reduced costs. In addition, current rapid-acting insulin analogues are not fast enough to control excessive postprandial glucose excursions in many patients. Biosimilar insulins demonstrated that are safe and effective, but interchangeability and automatic substitution remain an issue. Ultrafast-acting insulins should reduce postprandial hyperglycemia and improve flexibility in insulin dosing. This systematic review was conducted following widely recommended methods. We searched for each topic in Medline, Embase, the Cochrane Library, and SCISEARCH for relevant citations for the appropriate period. LY2963016 and MK-1293 are biosimilar insulins of insulin glargine, and SAR342434 is a biosimilar of insulin lispro. The abbreviated developed program demonstrated comparable efficacy and safety and supports their use for treatment of people with diabetes but no interchangeability. Faster-acting insulin aspart is a new formulation of insulin aspart with accelerated subcutaneous absorption. Faster aspart demonstrated noninferiority in reducing HbA1c as compared to insulin aspart with superiority in controlling postprandial hyperglycemia without increasing hypoglycemia, and flexible insulin dosing. Biosimilar insulins have comparable PK-PD profiles and equivalent efficacy and safety to original insulins at a lower price, making them available for more people with diabetes. Faster aspart is the first ultrafast-acting insulin. New upcoming clinical trials and more clinical experience with faster aspart will show the real potential of this new insulin.

Fast-Acting Insulin Aspart: The Rationale for a New Mealtime Insulin.

Attenuating postprandial hyperglycaemia is a critical factor in the achievement of optimal glucose control. Prandial insulin analogues have been developed to replicate the physiology of normal endogenous insulin secretion and action, with the aim of limiting postprandial glucose excursions. There is still, however, a significant unmet need, with many people failing to achieve desired glycaemic control targets despite the current armamentarium of prandial insulin analogues. Such insulins have a delayed onset and a longer duration of action than endogenous insulin production. There has been considerable focus on attempts to accelerate the time–action profile of prandial exogenous insulin in order to produce a more physiological profile. One such approach is to modify the insulin formulation. Fast-acting insulin aspart is a modified formulation of insulin aspart containing niacinamide and l-arginine. It has an earlier onset of action than aspart. In an extensive trial programme, this faster aspart demonstrated similar HbA1c reductions to those achieved with aspart but superior postprandial glucose reductions, with no increase in hypoglycaemia. Furthermore, administration of faster aspart up to 20 min after the start of a meal permitted similar glucose control to aspart given preprandially. These data, taken in totality, illustrate the potential role of faster insulin aspart in clinical practice.

Use of fast-acting insulin aspart in insulin pump therapy in clinical practice.

Fast‐acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) containing the additional excipients niacinamide and L‐arginine. The improved pharmacological profile and greater early glucose‐lowering action of faster aspart compared with IAsp suggests that faster aspart may be advantageous for people with diabetes using continuous subcutaneous insulin infusion (CSII). The recent onset 5 trial was the first to evaluate the efficacy and safety of an ultra‐fast‐acting insulin in CSII therapy in a large number of participants with type 1 diabetes (T1D). Non‐inferiority of faster aspart to IAsp in terms of change from baseline in HbA1c was confirmed, with an estimated treatment difference (ETD) of 0.09% (95% CI, 0.01; 0.17; P < 0.001 for non‐inferiority [0.4% margin]). Faster aspart was superior to IAsp in terms of change from baseline in 1‐hour post‐prandial glucose (PPG) increment after a meal test (ETD [95% CI], −0.91 mmol/L [−1.43; −0.39]; P = 0.001), with statistically significant improvements also at 30 minutes and 2 hours. The overall rate of severe or blood glucose‐confirmed hypoglycaemia was not statistically significantly different between treatments, with an estimated rate ratio of 1.00 (95% CI, 0.85; 1.16). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and the 4‐week run‐in periods (4 vs 0). Experience from clinical practice indicates that all pump settings should be reviewed when initiating faster aspart with CSII, and that the use of continuous glucose monitoring or flash glucose monitoring, along with a good understanding of meal content and bolus type, may also facilitate optimal use. This review summarizes the available clinical evidence for faster aspart administered via CSII and highlights practical considerations based on clinical experience that may help healthcare providers and individuals with T1D successfully initiate and adjust faster aspart with CSII.

Elucidating the Mechanism of Absorption of Fast-Acting Insulin Aspart: The Role of Niacinamide

PurposeFast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart containing two additional excipients: niacinamide, to increase early absorption, and L-arginine, to optimize stability. The aim of this study was to evaluate the impact of niacinamide on insulin aspart absorption and to investigate the mechanism of action underlying the accelerated absorption.MethodsThe impact of niacinamide was assessed in pharmacokinetic analyses in pigs and humans, small angle X-ray scattering experiments, trans-endothelial transport assays, vascular tension measurements, and subcutaneous blood flow imaging.ResultsNiacinamide increased the rate of early insulin aspart absorption in pigs, and pharmacokinetic modelling revealed this effect to be most pronounced up to ~30–40 min after injection in humans. Niacinamide increased the relative monomer fraction of insulin aspart by ~35%, and the apparent permeability of insulin aspart across an endothelial cell barrier by ~27%. Niacinamide also induced a concentration-dependent vasorelaxation of porcine arteries, and increased skin perfusion in pigs.ConclusionNiacinamide mediates the acceleration of initial insulin aspart absorption, and the mechanism of action appears to be multifaceted. Niacinamide increases the initial abundance of insulin aspart monomers and transport of insulin aspart after subcutaneous administration, and also mediates a transient, local vasodilatory effect.

Fast-Acting Insulin Aspart and the Need for New Mealtime Insulin Analogues in Adults With Type 1 and Type 2 Diabetes: A Canadian Perspective.

Limiting postprandial glucose (PPG) excursions is an important aspect of overall glycemic control. Rapid-acting insulin analogues (RAIAs) aim to mimic the physiologic action of endogenous insulin observed in individuals without diabetes and prevent excessive PPG excursions. However, many people with type 1 diabetes and type 2 diabetes treated with RAIAs do not achieve glycated hemoglobin (A1C) targets, and there is an unmet need for further improvements in PPG control. Current RAIAs have a delayed onset and a longer duration of action compared with endogenous insulin secreted in response to meals. Approachesto developing new mealtime insulins with accelerated absorption kinetics include changing the route of administration (i.e. via inhalation) and changing the insulin formulation. Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) containing the excipients niacinamide and L-arginine. Faster aspart has an earlier onset of insulin exposure and a greater early glucose-lowering effect than IAsp. In large clinical trials, mealtime faster aspart demonstrated noninferiority to IAsp with respect to A1C reduction and provided superior PPG control with no increase in overall severe or blood glucose-confirmed hyperglycemia. In addition, faster aspart administered up to 20min after the start of a meal was noninferior to mealtime IAsp in terms of A1C control, highlighting the opportunity for postmeal dosing. Faster aspart is the first of a new generation of mealtime insulins to be approved in Canada for the treatment of adults with type 1 diabetes and type 2 diabetes, and it is included in the 2018 Diabetes Canada clinical practice guidelines.

Clinical Pharmacology of Fast-Acting Insulin Aspart Versus Insulin Aspart Measured as Free or Total Insulin Aspart and the Relation to Anti-Insulin Aspart Antibody Levels in Subjects with Type 1 Diabetes Mellitus

BackgroundFast-acting insulin aspart (faster aspart) is an ultra-fast-acting formulation of insulin aspart (IAsp). This post hoc analysis investigated the pharmacokinetics of faster aspart versus IAsp, measured as free or total IAsp, and the relationship between anti-IAsp antibodies and the pharmacokinetics/pharmacodynamics of faster aspart and IAsp.MethodsFree and total IAsp concentrations and anti-IAsp antibodies were determined in adults with type 1 diabetes mellitus receiving subcutaneous faster aspart and/or IAsp in four single-dose clinical pharmacology trials (n = 175) and a 26-week phase IIIa trial (n = 1040). Pharmacodynamics were assessed by euglycaemic clamp or meal test, respectively.ResultsThe pharmacokinetic profile was left-shifted and early exposure was greater with faster aspart versus IAsp independent of free or total IAsp assay. The faster aspart-IAsp difference in the time to 50% of maximum IAsp concentration in the early part of the pharmacokinetic profile (tEarly 50 % Cmax) [95% confidence interval (CI)] was − 8.8 [− 10.0 to − 7.5] and − 7.6 [− 8.8 to − 6.4] min for free and total IAsp, respectively. The faster aspart/IAsp ratio for the area under the concentration–time curve (AUC) for IAsp from time zero to 30 min (AUCIAsp,0–30 min) [95% CI] was 1.88 [1.74–2.04] and 1.77 [1.64–1.90] for free and total IAsp. Higher anti-IAsp antibody levels were associated with a lower ratio of free/total IAsp for the total AUC for IAsp (AUCIAsp,0–t). Early glucose-lowering effect (AUC for the glucose infusion rate [GIR] from time zero to 60 min [AUCGIR,0–60 min]) was greater by 25–44% for faster aspart versus IAsp independent of anti-IAsp antibody levels. Total glucose-lowering effect (total AUC for GIR [AUCGIR,0–t]) in a clamp and 1-h postprandial glucose increment in a meal test appeared essentially unaffected by anti-IAsp antibodies.ConclusionsFaster aspart provides accelerated pharmacokinetics versus IAsp regardless if based on free or total IAsp assay. Higher anti-IAsp antibodies increase total IAsp concentrations but do not influence faster aspart nor IAsp pharmacodynamics.ClinicalTrials.gov identifiersNCT01618188, NCT02003677, NCT01934712, NCT02568280, NCT01831765.Electronic supplementary materialThe online version of this article (10.1007/s40262-018-0718-6) contains supplementary material, which is available to authorized users.

Pharmacological Properties of Faster-Acting Insulin Aspart.

Faster aspart is a new formulation of insulin aspart (IAsp) produced by adding the excipients niacinamide and L-arginine. As this new, "ultra-rapid insulin" is available in the EU-market and Canada, the pharmacokinetic and pharmacodynamics data is summarized. Faster aspart shows an earlier onset of appearance of insulin in the bloodstream after subcutaneous administration and an earlier onset of glucose-lowering action and a higher glycemic effect within the first 30min. Faster aspart administered by pump is indeed faster than conventional aspart with a faster on (-11min), faster off (-24min), and more than 100% greater insulin action within the first 30min. Tolerability of faster aspart is similar to that of Iasp; the same holds true for compatibility in pump use. Faster aspart shows a faster occurrence of insulin in the blood compared with IAsp in subcutaneous injection. Improvements over current analogs may be more pronounced in pumps than with injections. Data from phase IIIa studies confirm the reduction of postprandial glucose excursions that can be achieved with faster aspart.

Fiasp: a new faster‐acting insulin aspart formulation for diabetes

Fiasp is a new faster‐acting formulation of insulin aspart that is absorbed more quickly than conventional insulin aspart (NovoRapid) following mealtime administration. This article describes its properties, efficacy and adverse effects.

A Comparison of Pharmacokinetics and Pharmacodynamics of Biphasic Insulin Aspart 30, 50, 70 and Pure Insulin Aspart: A Randomized, Quadruple Crossover Study

The purpose of this study was to evaluate pharmacokinetic and pharmacodynamic profiles of pure insulin aspart and three different formulations of insulin aspart and protaminated insulin aspart: biphasic insulin aspart 30 (BIAsp30), biphasic insulin aspart 50 (BIAsp50) and biphasic insulin aspart 70 (BIAsp70). Nineteen type 1 diabetes patients received individually identical doses of the four different insulin aspart preparations on 4 separate days in this randomized crossover study. Having achieved overnight stable blood glucose control by intravenous infusions of human insulin, one of the trial insulins was injected subcutaneously and a standard meal was given in the morning. Plasma glucose and serum insulin aspart were recorded the following 12 hr. During the first 4 hr after injection with the trial insulin, the area under the curve for levels of insulin aspart (AUC(ins)) was significantly higher during insulin aspart treatment as compared to the other three insulin treatments, followed by BIAsp70, BIAsp50 and BIAsp30 (P < 0.05). Over the last 4 hr, the AUC(ins) for BIAsp30 was significantly higher as compared to the other insulin preparations (P < 0.05). By contrast, during the initial 4 hr, the area under the curve for levels of glucose (AUC(glu)) was highest after injection with BIAsp30 compared to the other three treatments (P < 0.05), while during the last 4 hr the highest AUC(glu) was seen following insulin aspart (P < 0.05). We conclude that when insulin aspart is pure or formulated with protamine in three different ratios, the pharmacokinetic profiles are readily distinguishable. These differences in pharmacokinetics are reflected in the pharmacodynamic profiles.

Postprandial versus preprandial dosing of biphasic insulin aspart in elderly type 2 diabetes patients

Preprandial dosing (within 5 min before meal) and postprandial dosing (15–20 min after meal onset) of NovoLog Mix 70/30 (BIAsp 30, a biphasic formulation of insulin aspart, 30% soluble and 70% protamine-crystallized) were compared in elderly (≥65 years) type 2 diabetes patients in this open-label, 12-week, crossover study. Ninety-three patients were treated with b.i.d. preprandial injections of BIAsp 30 during a 2-week run-in period and subsequently randomized to a 4-week treatment with either pre- or postprandial b.i.d. BIAsp 30, followed by crossover to the other regimen for 4 weeks. Mean plasma glucose values during a 4-h mealtest at the end of each treatment were similar for pre- and postprandial BIAsp 30 (153±58 mg/dl and 161±59 mg/dl, respectively, difference not significant). However, the mean blood glucose increment from self-measured blood glucose values was slightly but significantly greater after postprandial injection than after preprandial injection (treatment difference: 16.3 mg/dl; 95% CI: [0.5, 29.3]). Fifty-six percent of patients reported a hypoglycemic episode; postprandial injection did not increase the incidence of hypoglycemia as compared to preprandial injection (113 episodes versus 125 episodes, respectively). For some elderly type 2 diabetes patients, postprandial injection of BIAsp 30 may be an acceptable alternative to standard preprandial injection.