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Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart.

ABSTRACT: To evaluate the pharmacokinetics and pharmacodynamics of faster-acting insulin aspart and insulin aspart in a randomized, single-centre, double-blind study.Fifty-two patients with type 1 diabetes (mean age 40.3?years) received faster-acting insulin aspart, insulin aspart, or another faster aspart formulation (not selected for further development), each as a single 0.2?U/kg subcutaneous dose, under glucose-clamp conditions, in a three-way crossover design (3-12?days washout between dosing).Faster-acting insulin aspart had a faster onset of exposure compared with insulin aspart, shown by a 57% earlier onset of appearance [4.9 vs 11.2?min; ratio 0.43, 95% confidence interval (CI) 0.36; 0.51], a 35% earlier time to reach 50% maximum concentration (20.7 vs 31.6?min; ratio 0.65, 95% CI 0.59; 0.72) and a greater early exposure within 90?min after dosing. The greatest difference occurred during the first 15?min, when area under the serum insulin aspart curve was 4.5-fold greater with faster-acting insulin aspart than with insulin aspart. Both treatments had a similar time to maximum concentration, total exposure and maximum concentration. Faster-acting insulin aspart had a significantly greater glucose-lowering effect within 90?min after dosing [largest difference: area under the curve for the glucose infusion rate (AUC(GIR),?0-30?min) ratio 1.48, 95% CI 1.13; 2.02] and 17% earlier time to reach 50% maximum glucose infusion rate (38.3 vs 46.1?min; ratio 0.83, 95% CI 0.73; 0.94). The primary endpoint (AUC(GIR,?0-2?h)) was 10% greater for faster-acting insulin aspart, but did not reach statistical significance (ratio 1.10, 95% CI 1.00; 1.22). Both treatments had similar total and maximum glucose-lowering effects, indicating similar overall potency.Faster-acting insulin aspart was found to have earlier onset and higher early exposure than insulin aspart, and a greater early glucose-lowering effect, with similar potency.

SUBMITTER: Heise T

PROVIDER: S-EPMC5054830 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart.

Heise T T Hövelmann U U Brøndsted L L Adrian C L CL Nosek L L Haahr H H

Diabetes, obesity & metabolism 20150508 7

<h4>Aims</h4>To evaluate the pharmacokinetics and pharmacodynamics of faster-acting insulin aspart and insulin aspart in a randomized, single-centre, double-blind study.<h4>Methods</h4>Fifty-two patients with type 1 diabetes (mean age 40.3 years) received faster-acting insulin aspart, insulin aspart, or another faster aspart formulation (not selected for further development), each as a single 0.2 U/kg subcutaneous dose, under glucose-clamp conditions, in a three-way crossover design (3-12 days w ...[more]

PMID: 25846340

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Project description:BackgroundAbsorption 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.MethodsIn 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).ResultsConsistently 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.ConclusionThe 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. CLINICALTRIALS.Gov identifierNCT02033239.

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Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart.

Publications

Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart.

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