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Hanne Haahr - One of the best experts on this subject based on the ideXlab platform.
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Fast-Acting Insulin Aspart: A Review of its Pharmacokinetic and Pharmacodynamic Properties and the Clinical Consequences
Clinical Pharmacokinetics, 2020Co-Authors: Hanne Haahr, Tim HeiseAbstract:Fast-acting Insulin Aspart (faster Aspart) is Insulin Aspart (IAsp) with two added excipients, l -arginine and niacinamide, to ensure formulation stability with accelerated initial absorption after subcutaneous administration compared with previously developed rapid-acting Insulins. The pharmacokinetic/pharmacodynamic properties of faster Aspart have been characterised in clinical pharmacology trials with comparable overall methodology. In subjects with type 1 (T1D) or type 2 (T2D) diabetes, the serum IAsp concentration–time and glucose-lowering effect profiles are left-shifted for faster Aspart compared with IAsp. In addition, faster Aspart provides earlier onset, doubling of initial exposure, and an up to 2.5-fold increase in initial glucose-lowering effect within 30 min of subcutaneous injection, as well as earlier offset of exposure and effect. Similar results have been shown using continuous subcutaneous Insulin infusion (CSII). The improved pharmacological properties of faster Aspart versus IAsp are consistent across populations, i.e. in the elderly, children, adolescents and the Japanese. Thus, the faster Aspart pharmacological characteristics more closely resemble the mealtime Insulin secretion in healthy individuals, giving faster Aspart the potential to further improve postprandial glucose control in subjects with diabetes. Indeed, change from baseline in 1-h postprandial glucose increment is in favour of faster Aspart versus IAsp when used as basal-bolus or CSII treatment in phase III trials in subjects with T1D or T2D. This review summarises the currently published results from clinical pharmacology trials with faster Aspart and discusses the potential clinical benefits of faster Aspart compared with previous rapid-acting Insulin products.
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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
Clinical Pharmacokinectics, 2019Co-Authors: Hanne Haahr, Thomas R Pieber, Chantal Mathieu, Theis Gondolf, Masanari Shiramoto, Lars Erichsen, Tim HeiseAbstract:Fast-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. Free 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. The 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. Faster 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. NCT01618188, NCT02003677, NCT01934712, NCT02568280, NCT01831765.
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greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast acting Insulin Aspart compared with Insulin Aspart
Diabetes Obesity and Metabolism, 2018Co-Authors: Ananda Basu, Thomas R Pieber, Lars Erichsen, Ann Kathrine Hansen, Stefanie Sachfriedl, Rita Basu, Hanne HaahrAbstract:AIM To investigate the mechanisms behind the lower postprandial glucose (PPG) concentrations achieved with fast-acting Insulin Aspart (faster Aspart) than with Insulin Aspart (IAsp). MATERIALS AND METHODS In a randomized, double-blind, crossover trial, 41 people with type 1 diabetes received identical subcutaneous single faster Aspart and IAsp doses (individualized for each participant), together with a standardized mixed meal (including 75 g carbohydrate labelled with [1-13 C] glucose). PPG turnover was determined by the triple-tracer meal method using continuous, variable [6-3 H] glucose and [6,6-2 H2 ] glucose infusion. RESULTS Insulin exposure within the first hour was 32% greater with faster Aspart than with IAsp (treatment ratio faster Aspart/IAsp 1.32 [95% confidence interval {CI} 1.18;1.48]; P < .001), leading to a 0.59-mmol/L non-significantly smaller PPG increment at 1 hour (ΔPG1h ; treatment difference faster Aspart-IAsp -0.59 mmol/L [95% CI -1.19; 0.01]; P = .055). The trend towards reduced ΔPG1h with faster Aspart was attributable to 12% greater suppression of endogenous glucose production (EGP; treatment ratio 1.12 [95% CI 1.01; 1.25]; P = .040) and 23% higher glucose disappearance (1.23 [95% CI 1.05; 1.45]; P = .012) with faster Aspart than with IAsp during the first hour. Suppression of free fatty acid levels during the first hour was 36% greater for faster Aspart than for IAsp (1.36 [95% CI 1.01;1.88]; P = .042). CONCLUSIONS The trend towards improved PPG control with faster Aspart vs IAsp in this study was attributable to both greater early suppression of EGP and stimulation of glucose disappearance.
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faster acting Insulin Aspart provides faster onset and greater early exposure vs Insulin Aspart in children and adolescents with type 1 diabetes mellitus
Pediatric Diabetes, 2017Co-Authors: Maryam Fath, Thomas Danne, Lars Erichsen, Torben Biester, Olga Kordonouri, Hanne HaahrAbstract:1 Background Faster-acting Insulin Aspart (faster Aspart) is Insulin Aspart (IAsp) in a new formulation with additional excipients (L-arginine and niacinamide). In adults, faster Aspart provides faster onset and greater early exposure and action vs IAsp. 2 Aim This randomized, double-blind, 2-period crossover trial investigated the pharmacological properties of faster Aspart vs IAsp in 12 children (6-11 years), 13 adolescents (12-17 years), and 15 adults (18-64 years) with type 1 diabetes mellitus. 3 Methods Subjects received 0.2 U/kg subcutaneous dosing (mean of 8.3, 12.8, and 15.6 U, respectively) immediately prior to a standardized meal (17.3 g carbohydrate/100 mL; amount adjusted by body weight). 4 Results Consistently across age groups, onset of appearance occurred approximately twice-as-fast (5-7 minutes earlier) and early exposure (AUCIAsp ,0-30min; area under the IAsp curve from 0 to 30 minutes) was greater (by 78%-147%) for faster Aspart vs IAsp, with no treatment differences in total exposure (AUCIAsp ,0-t) or maximum concentration (C max). Two-hour postmeal plasma glucose excursion was reduced for faster Aspart vs IAsp (although only reaching statistical significance in children). In accordance with the absolute dose administered for each age group, AUCIAsp ,0-t for faster Aspart was lower in children (estimated ratio children/adults [95% confidence interval]: 0.59 [0.50;0.69], P < .001) and adolescents (0.78 [0.67;0.90], P = .002) vs adults. No age group differences were seen in C max (0.91 [0.70;1.17], P = .445, and 0.99 [0.77;1.26], P = .903). The age effect on AUCIAsp ,0-t and C max did not differ statistically significantly between treatments. Faster Aspart and IAsp were well-tolerated. 5 Conclusion The current findings in children and adolescents suggest a potential for faster Aspart to improve postprandial glycemia over current rapid-acting Insulins also in younger age groups. http://ClinicalTrials.gov identifier: NCT02035371.
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pharmacokinetic and pharmacodynamic properties of faster acting Insulin Aspart versus Insulin Aspart across a clinically relevant dose range in subjects with type 1 diabetes mellitus
Clinical Pharmacokinectics, 2017Co-Authors: Tim Heise, Ulrike Hovelmann, Leszek Nosek, Kirstine Stenderpetersen, Jacob Bonde Jacobsen, Eric Zijlstra, Hanne HaahrAbstract:Absorption of current rapid-acting Insulins is too slow for patients with diabetes mellitus to achieve optimal postprandial glucose control. Faster-acting Insulin Aspart (faster Aspart) is Insulin Aspart in a new formulation with faster early absorption. We compared the pharmacokinetic/pharmacodynamic properties of faster Aspart and Insulin Aspart across a clinically relevant dose range. In this randomised, double-blind, crossover trial, 46 subjects with type 1 diabetes mellitus received single subcutaneous doses of faster Aspart and Insulin Aspart at 0.1, 0.2 (repeated three times to estimate within-subject variability) and 0.4 U/kg in a euglycaemic clamp setting (target 5.5 mmol/L). Consistently for the three doses, faster Aspart demonstrated faster onset and greater early absorption and glucose-lowering effect versus Insulin Aspart. Across all three doses, onset of appearance occurred approximately twice as fast (approximately 5 min earlier) and early Insulin exposure (AUCIAsp,0–30min) was approximately 1.5- to 2-fold greater for faster Aspart versus Insulin Aspart. Likewise, onset of action occurred approximately 5 min faster and early glucose-lowering effect (AUCGIR,0–30min) was approximately 1.5- to 2-fold larger for faster Aspart versus Insulin Aspart. Relative bioavailability was approximately 100% and total glucose-lowering effect was similar for faster Aspart versus Insulin Aspart. Dose–concentration and dose–response relationships were comparable between faster Aspart and Insulin Aspart. Within-subject variability in glucose-lowering effect was low for faster Aspart (coefficient of variation approximately 20%) and not significantly different from Insulin Aspart. The faster onset and greater early Insulin exposure and glucose-lowering effect with faster Aspart versus Insulin Aspart are preserved across a broad range of doses and consistently observed from day to day. NCT02033239.
Tim Heise - One of the best experts on this subject based on the ideXlab platform.
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Fast-Acting Insulin Aspart: A Review of its Pharmacokinetic and Pharmacodynamic Properties and the Clinical Consequences
Clinical Pharmacokinetics, 2020Co-Authors: Hanne Haahr, Tim HeiseAbstract:Fast-acting Insulin Aspart (faster Aspart) is Insulin Aspart (IAsp) with two added excipients, l -arginine and niacinamide, to ensure formulation stability with accelerated initial absorption after subcutaneous administration compared with previously developed rapid-acting Insulins. The pharmacokinetic/pharmacodynamic properties of faster Aspart have been characterised in clinical pharmacology trials with comparable overall methodology. In subjects with type 1 (T1D) or type 2 (T2D) diabetes, the serum IAsp concentration–time and glucose-lowering effect profiles are left-shifted for faster Aspart compared with IAsp. In addition, faster Aspart provides earlier onset, doubling of initial exposure, and an up to 2.5-fold increase in initial glucose-lowering effect within 30 min of subcutaneous injection, as well as earlier offset of exposure and effect. Similar results have been shown using continuous subcutaneous Insulin infusion (CSII). The improved pharmacological properties of faster Aspart versus IAsp are consistent across populations, i.e. in the elderly, children, adolescents and the Japanese. Thus, the faster Aspart pharmacological characteristics more closely resemble the mealtime Insulin secretion in healthy individuals, giving faster Aspart the potential to further improve postprandial glucose control in subjects with diabetes. Indeed, change from baseline in 1-h postprandial glucose increment is in favour of faster Aspart versus IAsp when used as basal-bolus or CSII treatment in phase III trials in subjects with T1D or T2D. This review summarises the currently published results from clinical pharmacology trials with faster Aspart and discusses the potential clinical benefits of faster Aspart compared with previous rapid-acting Insulin products.
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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
Clinical Pharmacokinectics, 2019Co-Authors: Hanne Haahr, Thomas R Pieber, Chantal Mathieu, Theis Gondolf, Masanari Shiramoto, Lars Erichsen, Tim HeiseAbstract:Fast-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. Free 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. The 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. Faster 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. NCT01618188, NCT02003677, NCT01934712, NCT02568280, NCT01831765.
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investigation of pump compatibility of fast acting Insulin Aspart in subjects with type 1 diabetes
Journal of diabetes science and technology, 2018Co-Authors: Eric Zijlstra, Tim Heise, Leszek Nosek, Marek Demissie, Tina Graungaard, Bruce W. BodeAbstract:Background:Ultra-fast-acting Insulins, such as fast-acting Insulin Aspart (faster Aspart), have pharmacokinetic properties that may be advantageous for patients using continuous subcutaneous insuli...
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investigation of pump compatibility of fast acting Insulin Aspart in subjects with type 1 diabetes
Journal of diabetes science and technology, 2018Co-Authors: Eric Zijlstra, Tim Heise, Leszek Nosek, Marek Demissie, Tina Graungaard, Bruce W. BodeAbstract:Background:Ultra-fast-acting Insulins, such as fast-acting Insulin Aspart (faster Aspart), have pharmacokinetic properties that may be advantageous for patients using continuous subcutaneous Insulin infusion (CSII), provided that they are compatible with and safe to use in CSII.Methods:Randomized, double-blind, parallel-group, actively controlled trial evaluating compatibility, efficacy, and safety of faster Aspart in adults with type 1 diabetes using their own MiniMed Paradigm pump with Quick-Set or Silhouette infusion sets. Following run-in, subjects were randomized (2:1) to faster Aspart (n = 25) or Insulin Aspart (n = 12) for 6 weeks. Primary endpoint was the number of microscopically confirmed episodes of infusion-set occlusions.Results:No microscopically confirmed episodes of infusion-set occlusions were observed in either arm. Seven possible infusion-set occlusions were reported by five subjects (all faster Aspart); none were prompted by a plug observed by the subject (prompted by unexplained hyper...
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pharmacokinetic and pharmacodynamic properties of faster acting Insulin Aspart versus Insulin Aspart across a clinically relevant dose range in subjects with type 1 diabetes mellitus
Clinical Pharmacokinectics, 2017Co-Authors: Tim Heise, Ulrike Hovelmann, Leszek Nosek, Kirstine Stenderpetersen, Jacob Bonde Jacobsen, Eric Zijlstra, Hanne HaahrAbstract:Absorption of current rapid-acting Insulins is too slow for patients with diabetes mellitus to achieve optimal postprandial glucose control. Faster-acting Insulin Aspart (faster Aspart) is Insulin Aspart in a new formulation with faster early absorption. We compared the pharmacokinetic/pharmacodynamic properties of faster Aspart and Insulin Aspart across a clinically relevant dose range. In this randomised, double-blind, crossover trial, 46 subjects with type 1 diabetes mellitus received single subcutaneous doses of faster Aspart and Insulin Aspart at 0.1, 0.2 (repeated three times to estimate within-subject variability) and 0.4 U/kg in a euglycaemic clamp setting (target 5.5 mmol/L). Consistently for the three doses, faster Aspart demonstrated faster onset and greater early absorption and glucose-lowering effect versus Insulin Aspart. Across all three doses, onset of appearance occurred approximately twice as fast (approximately 5 min earlier) and early Insulin exposure (AUCIAsp,0–30min) was approximately 1.5- to 2-fold greater for faster Aspart versus Insulin Aspart. Likewise, onset of action occurred approximately 5 min faster and early glucose-lowering effect (AUCGIR,0–30min) was approximately 1.5- to 2-fold larger for faster Aspart versus Insulin Aspart. Relative bioavailability was approximately 100% and total glucose-lowering effect was similar for faster Aspart versus Insulin Aspart. Dose–concentration and dose–response relationships were comparable between faster Aspart and Insulin Aspart. Within-subject variability in glucose-lowering effect was low for faster Aspart (coefficient of variation approximately 20%) and not significantly different from Insulin Aspart. The faster onset and greater early Insulin exposure and glucose-lowering effect with faster Aspart versus Insulin Aspart are preserved across a broad range of doses and consistently observed from day to day. NCT02033239.
Takashi Kadowaki - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of fast acting Insulin Aspart compared with Insulin Aspart in combination with Insulin degludec in japanese adults with type 1 diabetes a subgroup analysis of the randomized onset 8 trial
Endocrine Journal, 2020Co-Authors: Mitsuhisa Komatsu, Magnus Ekelund, Hiroshi Horio, Takashi KadowakiAbstract:This study aimed to confirm the efficacy and safety of mealtime and post-meal fast-acting Insulin Aspart versus Insulin Aspart, both with basal Insulin degludec, in Japanese patients with type 1 diabetes. This was a subgroup analysis of onset 8, a randomized multicenter, treat-to-target trial of mealtime fast-acting Insulin Aspart (subgroup n = 73), mealtime Insulin Aspart (n = 83), or open-label post-meal fast-acting Insulin Aspart (n = 89), all for 26 weeks. Change from baseline in HbA1c was considered the primary endpoint. After 26 weeks, the estimated treatment difference (ETD, 95% CI) for change from baseline in HbA1c between mealtime fast-acting Insulin Aspart or post-meal fast-acting Insulin Aspart vs. Insulin Aspart was 0.01% (-0.16;0.19) and 0.10% (-0.07;0.27), respectively. Following a standardized meal test, ETD for change from baseline in postprandial glucose (PPG) increment at 1 hour was -16.91 mg/dL (-32.15;-1.68) for mealtime fast-acting Insulin Aspart and 40.16 mg/dL (25.46;54.87) for post-meal fast-acting Insulin Aspart, both versus Insulin Aspart. Mean self-measured blood glucose 1-hour PPG increments also showed a trend towards improved PPG control with mealtime fast-acting Insulin Aspart versus Insulin Aspart. Rates of overall hypoglycemia (35.56, 37.72 and 38.75 per patient-year of exposure with mealtime fast-acting Insulin Aspart, post-meal fast-acting Insulin Aspart and Insulin Aspart, respectively) and meal-related hypoglycemia were similar between treatment arms. Consistent with findings of onset 8, this analysis confirmed mealtime and post-meal fast-acting Insulin Aspart provided effective HbA1c and PPG control versus Insulin Aspart, with similar safety profiles, in Japanese adults with type 1 diabetes.
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fast acting Insulin Aspart versus Insulin Aspart in the setting of Insulin degludec treated type 1 diabetes efficacy and safety from a randomized double blind trial
Diabetes Obesity and Metabolism, 2018Co-Authors: John B Buse, Mitsuhisa Komatsu, Hiroshi Horio, Anders L Carlson, Ofri Mosenzon, Ludger Rose, Bo Liang, Kristine Buchholtz, Takashi KadowakiAbstract:Aim To evaluate the efficacy and safety of mealtime or post‐meal fast‐acting Insulin Aspart (faster Aspart) vs mealtime Insulin Aspart (IAsp), both in combination with Insulin degludec, in participants with type 1 diabetes (T1D).
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fast acting Insulin Aspart versus Insulin Aspart in the setting of Insulin degludec treated type 1 diabetes efficacy and safety from a randomized double blind trial
Diabetes Obesity and Metabolism, 2018Co-Authors: John B Buse, Mitsuhisa Komatsu, Hiroshi Horio, Ofri Mosenzon, Ludger Rose, Bo Liang, Kristine Buchholtz, Anders Carlson, Takashi KadowakiAbstract:AIM To evaluate the efficacy and safety of mealtime or post-meal fast-acting Insulin Aspart (faster Aspart) vs mealtime Insulin Aspart (IAsp), both in combination with Insulin degludec, in participants with type 1 diabetes (T1D). METHODS This multicentre, treat-to-target trial (Clinical trial registry: NCT02500706, ClinicalTrials.gov) randomized participants to double-blind mealtime faster Aspart (n = 342) or IAsp (n = 342) or open-label post-meal faster Aspart (n = 341). The primary endpoint was change from baseline in HbA1c 26 weeks post randomization. All available information, regardless of treatment discontinuation, was used for evaluation of the effect. RESULTS Non-inferiority for the change from baseline in HbA1c was confirmed for mealtime and post-meal faster Aspart vs IAsp (estimated treatment difference [ETD]: 95%CI, -0.02% [-0.11; 0.07] and 0.10% [0.004; 0.19], respectively). Mealtime faster Aspart was superior to IAsp for 1-hour PPG increment using a meal test (ETD, -0.90 mmol/L [-1.36; -0.45]; P < 0.001). Self-monitored 1-hour PPG increment favoured faster Aspart at breakfast (ETD, -0.58 mmol/L [-0.99; -0.17]; P = 0.006) and across all meals (-0.48 mmol/L [-0.74; -0.21]; P < 0.001). Safety profiles and overall rate of severe or blood glucose-confirmed hypoglycaemia were similar between treatments, but significantly less hypoglycaemia was seen 3 to 4 hours after meals with mealtime faster Aspart. CONCLUSION Mealtime and post-meal faster Aspart in conjunction with Insulin degludec provided effective glycaemic control compared with IAsp, with no increased safety risk. Mealtime faster Aspart provided PPG control superior to that of IAsp.
Malgorzata E Wilinska - One of the best experts on this subject based on the ideXlab platform.
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hybrid closed loop glucose control with faster Insulin Aspart compared with standard Insulin Aspart in adults with type 1 diabetes a double blind multicentre multinational randomized crossover study
Diabetes Obesity and Metabolism, 2021Co-Authors: David Herzig, Malgorzata E Wilinska, Charlotte K Boughton, Sara Hartnell, Hood Thabit, Tina Poettler, Nicole L Ashcroft, Judy SibayanAbstract:Objective: We evaluated hybrid closed-loop glucose control with faster-acting Insulin Aspart (Fiasp) in adults with type 1 diabetes (T1D). We hypothesised that closed-loop with Fiasp provides similar efficacy as closed-loop with standard Insulin Aspart. Research design and methods: In a double-blind, multinational, randomised, crossover study, 25 adults with T1D using Insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4 ± 0.8% [57 ± 8 mmol/mol]) underwent two 8-week periods of unrestricted living comparing hybrid closed-loop with Fiasp and hybrid closed-loop with standard Insulin Aspart in random order. During both interventions, the CamAPS FX closed-loop system incorporating Cambridge model predictive control algorithm was used. Results: In an intention-to-treat analysis, the proportion of time sensor glucose was in target range (3.9-10.0 mmol/L; primary endpoint) was not different between interventions (75 ± 8% vs. 75 ± 8% for hybrid closed-loop with Fiasp vs. hybrid closed-loop with standard Insulin Aspart; mean-adjusted difference - 0.6 [95%CI -1.8 to 0.7%]; P < 0.001 for non-inferiority [non-inferiority margin 5%]). The proportion of time with sensor glucose <3.9 mmol/L (median [IQR] 2.4 [1.2-3.2%] vs. 2.9 [1.7-4.0%]; P = 0.01) and < 3.0 mmol/L (median [IQR] 0.4 [0.2-0.7%] vs. 0.7 [0.2-0.9%]; P = 0.03) was reduced with Fiasp vs. standard Insulin Aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. 8.0 ± 0.8 mmol/L; P = 0.13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; P = 0.90). Total daily Insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; P = 0.45). No severe hypoglycaemia or ketoacidosis occurred. Conclusions: The use of Fiasp in CamAPS FX closed-loop system may reduce hypoglycaemia without compromising glucose control compared to standard Insulin Aspart in adults with T1D. This article is protected by copyright. All rights reserved.
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short term fully closed loop Insulin delivery using faster Insulin Aspart compared with standard Insulin Aspart in type 2 diabetes
Diabetes Obesity and Metabolism, 2019Co-Authors: Lia Bally, David Herzig, Yue Ruan, Malgorzata E Wilinska, Mariam Semmo, Andreas Vogt, Maria M Wertli, Bruno Vogt, Christoph StettlerAbstract:We evaluated the efficacy and safety of short-term fully closed-loop Insulin delivery using faster versus standard Insulin Aspart in type 2 diabetes. Fifteen adults with Insulin-treated type 2 diabetes underwent 22 hours of closed-loop Insulin delivery with either faster or standard Insulin Aspart in a double-blind randomised crossover design. Basal-bolus regimen was replaced by model predictive control algorithm-directed Insulin delivery based on sensor glucose levels. The primary outcome was time with plasma glucose in target range (5.6-10.0mmol/l) and did not differ between treatments (mean difference [95%CI] -3.3% [8.2;1.7], p=0.17). Mean glucose and glucose variability were comparable, as was time spent below and above target range. Hypoglycaemia (<3.5mmol/l) occurred once with faster Insulin Aspart and twice with standard Insulin Aspart. Mean total Insulin dose was higher with faster Insulin Aspart (mean difference [95%CI] 3.7U [0.7;6.8], p=0.021). No episodes of severe hypoglycaemia or other serious adverse events occurred. In conclusion, short-term fully closed-loop in type 2 diabetes may require higher dose of faster Insulin Aspart compared to standard Insulin Aspart to achieve comparable glucose control. This article is protected by copyright. All rights reserved.
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pharmacokinetics of diluted u20 Insulin Aspart compared with standard u100 in children aged 3 6 years with type 1 diabetes during closed loop Insulin delivery a randomised clinical trial
Diabetologia, 2015Co-Authors: Yue Ruan, Malgorzata E Wilinska, Daniela Elleri, Janet M Allen, Martin Tauschmann, David B DungerAbstract:Aims/hypothesis The aim of this study was to compare the pharmacokinetics of two different concentrations of Insulin Aspart (B28Asp human Insulin) in children aged 3–6 years with type 1 diabetes.
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pharmacokinetics of Insulin Aspart in pump treated subjects with type 1 diabetes reproducibility and effect of age weight and duration of diabetes
Diabetes Care, 2013Co-Authors: Ahmad Haidar, Malgorzata E Wilinska, Daniela Elleri, Janet M Allen, Kavita Kumareswaran, Lalantha Leelarathna, Karen Caldwell, Helen R Murphy, Carlo L Acerini, Mark L EvansAbstract:Insulin Aspart, lispro, or glulisine are recommended in pump-treated type 1 diabetes (T1D). Aspart pharmacokinetics has been studied (1), but little is known about its reproducibility and associations with anthropometric and clinical factors. We analyzed retrospectively data collected in 70 pump-treated subjects with T1D, comprising 39 females, 46 young, with mean (SD) BMI 22.7 (4.2) kg/m2, A1C 8.1% (1.3) (65.3 [14.4] mmol/mol), and total daily Insulin 0.8 (0.3) units/kg/day, who were undergoing investigations, with ethical approval, of closed-loop Insulin delivery. Participants/guardians signed consent/assent as appropriate. Participants were admitted twice to the research facility, 1–6 weeks apart, for 15–37 h, and consumed 1–4 meals accompanied by prandial Insulin Aspart. Basal Aspart was delivered using closed-loop Insulin delivery or conventional pump therapy. Venous blood samples were collected every 30–60 min to measure plasma Insulin (Invitron, Monmouth, U.K.). From 5,804 plasma Insulin measurements, we estimated, using a two-compartment model, the time-to-peak plasma Insulin concentration ( t max [min]), the metabolic clearance rate of Insulin (MCR in mL/kg/min), and the background residual plasma Insulin concentration (mU/L). Results are …
David Herzig - One of the best experts on this subject based on the ideXlab platform.
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hybrid closed loop glucose control with faster Insulin Aspart compared with standard Insulin Aspart in adults with type 1 diabetes a double blind multicentre multinational randomized crossover study
Diabetes Obesity and Metabolism, 2021Co-Authors: David Herzig, Malgorzata E Wilinska, Charlotte K Boughton, Sara Hartnell, Hood Thabit, Tina Poettler, Nicole L Ashcroft, Judy SibayanAbstract:Objective: We evaluated hybrid closed-loop glucose control with faster-acting Insulin Aspart (Fiasp) in adults with type 1 diabetes (T1D). We hypothesised that closed-loop with Fiasp provides similar efficacy as closed-loop with standard Insulin Aspart. Research design and methods: In a double-blind, multinational, randomised, crossover study, 25 adults with T1D using Insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4 ± 0.8% [57 ± 8 mmol/mol]) underwent two 8-week periods of unrestricted living comparing hybrid closed-loop with Fiasp and hybrid closed-loop with standard Insulin Aspart in random order. During both interventions, the CamAPS FX closed-loop system incorporating Cambridge model predictive control algorithm was used. Results: In an intention-to-treat analysis, the proportion of time sensor glucose was in target range (3.9-10.0 mmol/L; primary endpoint) was not different between interventions (75 ± 8% vs. 75 ± 8% for hybrid closed-loop with Fiasp vs. hybrid closed-loop with standard Insulin Aspart; mean-adjusted difference - 0.6 [95%CI -1.8 to 0.7%]; P < 0.001 for non-inferiority [non-inferiority margin 5%]). The proportion of time with sensor glucose <3.9 mmol/L (median [IQR] 2.4 [1.2-3.2%] vs. 2.9 [1.7-4.0%]; P = 0.01) and < 3.0 mmol/L (median [IQR] 0.4 [0.2-0.7%] vs. 0.7 [0.2-0.9%]; P = 0.03) was reduced with Fiasp vs. standard Insulin Aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. 8.0 ± 0.8 mmol/L; P = 0.13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; P = 0.90). Total daily Insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; P = 0.45). No severe hypoglycaemia or ketoacidosis occurred. Conclusions: The use of Fiasp in CamAPS FX closed-loop system may reduce hypoglycaemia without compromising glucose control compared to standard Insulin Aspart in adults with T1D. This article is protected by copyright. All rights reserved.
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pharmacokinetics of faster and standard Insulin Aspart during fully closed loop Insulin delivery in type 2 diabetes
Diabetes Technology & Therapeutics, 2020Co-Authors: David Herzig, Lia Bally, Christoph Stettler, Joachim Dehais, Jeanchristophe Prost, Christos T Nakas, Roman HovorkaAbstract: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 ...
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short term fully closed loop Insulin delivery using faster Insulin Aspart compared with standard Insulin Aspart in type 2 diabetes
Diabetes Obesity and Metabolism, 2019Co-Authors: Lia Bally, David Herzig, Yue Ruan, Malgorzata E Wilinska, Mariam Semmo, Andreas Vogt, Maria M Wertli, Bruno Vogt, Christoph StettlerAbstract:We evaluated the efficacy and safety of short-term fully closed-loop Insulin delivery using faster versus standard Insulin Aspart in type 2 diabetes. Fifteen adults with Insulin-treated type 2 diabetes underwent 22 hours of closed-loop Insulin delivery with either faster or standard Insulin Aspart in a double-blind randomised crossover design. Basal-bolus regimen was replaced by model predictive control algorithm-directed Insulin delivery based on sensor glucose levels. The primary outcome was time with plasma glucose in target range (5.6-10.0mmol/l) and did not differ between treatments (mean difference [95%CI] -3.3% [8.2;1.7], p=0.17). Mean glucose and glucose variability were comparable, as was time spent below and above target range. Hypoglycaemia (<3.5mmol/l) occurred once with faster Insulin Aspart and twice with standard Insulin Aspart. Mean total Insulin dose was higher with faster Insulin Aspart (mean difference [95%CI] 3.7U [0.7;6.8], p=0.021). No episodes of severe hypoglycaemia or other serious adverse events occurred. In conclusion, short-term fully closed-loop in type 2 diabetes may require higher dose of faster Insulin Aspart compared to standard Insulin Aspart to achieve comparable glucose control. This article is protected by copyright. All rights reserved.