A pooled analysis of clinical pharmacology trials investigating the pharmacokinetic and pharmacodynamic characteristics of fast-acting insulin aspart in adults with type 1 diabetes
Open accessAbstract
Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation aiming to mimic the fast endogenous prandial insulin release more closely than currently available insulin products. In a post hoc analysis of pooled data from six clinical pharmacology trials, the pharmacological characteristics of faster aspart and IAsp were compared. The analysis included 218 adult subjects with type 1 diabetes from six randomised, double-blind, crossover trials in the faster aspart clinical development programme. Subjects received subcutaneous dosing (0.2 U/kg) of faster aspart and IAsp. In three trials, a 12-h euglycaemic clamp was performed (target 5.5 mmol/L; 100 mg/dL) to assess pharmacodynamics. The pharmacokinetic and pharmacodynamic profiles were left-shifted for faster aspart versus IAsp. Onset of appearance occurred 4.9 min earlier (95% confidence interval [CI] faster aspart-IAsp: [−5.3 to −4.4], p < 0.001), early exposure (AUCIAsp,0–30min) was two times greater (estimated ratio faster aspart/IAsp 2.01 [1.87–2.17], p < 0.001) and offset of exposure (t Late 50% Cmax) occurred 12.2 min earlier [−17.9 to −6.5] (p < 0.001) for faster aspart versus IAsp. Accordingly, onset of action occurred 4.9 min earlier [−6.9 to −3.0] (p < 0.001), early glucose-lowering effect (AUCGIR,0–30min) was 74% greater (1.74 [1.47–2.10], p < 0.001) and offset of glucose-lowering effect (t Late 50% GIRmax) occurred 14.3 min earlier [−22.1 to −6.5] (p < 0.001) for faster aspart versus IAsp. Total exposure and total glucose-lowering effect did not differ significantly between treatments. Faster aspart has the potential to better mimic the physiologic prandial insulin secretion and thereby to improve postprandial glucose control compared with IAsp. ClinicalTrials.gov identifiers: NCT02035371, NCT01924637, NCT02131246, NCT02033239, NCT02003677, NCT01618188.
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Two injectable ultra-rapid-acting analog (URAA) insulin formulations are available that contain excipients that accelerate absorption and provide more activity in the first portion of their profile compared with the other RAA.
“Two injectable ultra-rapid-acting analog (URAA) insulin formulations are available that contain excipients that accelerate absorption and provide more activity in the first portion of their profile compared with the other RAA (8,9).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [9]
The Introduction describes one injectable formulation, faster aspart, and says its added niacinamide accelerates initial absorption. The Results report greater early glucose-lowering activity than insulin aspart in adults with type 1 diabetes. This paper does not establish that two such formulations are available or compare faster aspart with other rapid-acting analogs beyond insulin aspart. Page numbers were not supplied for these passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFaster-acting insulin aspart has a quicker onset and offset than regular insulin aspart and offers better control of postmeal glucose spikes and less hypoglycaemia 2-5 h after a meal.
“Fasteracting insulin aspart has a quicker onset and offset than regular insulin aspart and offers better control of postmeal glucose spikes and less hypoglycaemia 2-5 h after a meal.80”
From The future of type 1 diabetes therapy (2025) · cites this paper as [80]
The Conclusions report faster onset and earlier offset than insulin aspart, and the Discussion reports better postprandial glucose control in meal tests. The Discussion says earlier offset may reduce late postprandial hypoglycaemia, but it does not establish less hypoglycaemia 2–5 hours after a meal. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThis finding aligns with those of previous clinical trials that showed faster-acting insulins improve postprandial glucose without compromising overall glycaemic management or safety.
“This finding aligns with those of previous clinical trials that showed fasteracting insulins improve postprandial glucose without compromising overall glycaemic management or safety.80,81”
From The future of type 1 diabetes therapy (2025) · cites this paper as [80]
Results from comparative effectiveness meta-analyses suggest that each new class of oral noninsulin agents when added to metformin generally lowers A1C by approximately 0.7-1.0% (8-11 mmol/mol).
“Results from comparative effectiveness meta-analyses suggest that each new class of oral noninsulin agents when added to metformin generally lowers A1C by approximately 0.7-1.0%(8-11 mmol/mol).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [9]
The Results section compares the glucose-lowering effects of two insulin aspart formulations in adults with type 1 diabetes. Searches for oral noninsulin agents added to metformin, comparative-effectiveness meta-analyses, and the stated A1C reduction found no passage addressing the claim. Page numbers are not available in our copy. (LLM, conf=0.78)
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9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025
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The evolution of insulin and how it informs therapy and treatment choices
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The future of type 1 diabetes therapy
Ziegler, A.-G., Cengiz, E., & Kay, T. W. H. (2025) · The Lancet · doi:10.1016/s0140-6736(25)01438-2 · Cited by 42 · see citing works
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- Authors
- Heise, T., Pieber, T. R., Danne, T., Erichsen, L., & Haahr, H.
- Affiliations
- Profil Institute for Metabolic Research (DE)
- Medical University of Graz (AT)
- Kinderkrankenhaus auf der Bult (DE)
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Heise, Tim
- Venue
- Clinical Pharmacokinetics
- Published
- 2017-02-15
- Volume
- 56
- Issue
- 5
- Pages
- 551-559
- ISSN
- 0312-5963 (ISSN-L)
- 1179-1926
- PMC
- PMC5385193
- OpenAlex
- W2587826249
- Cited by
- 182
- References
- 6
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 12 · 2023: 18 · 2022: 21 · 2021: 22 · 2020: 28 · 2019: 28 · 2018: 18 · 2017: 15 · 2016: 1
- FWCI
- 19.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Pharmacokinetics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- fast-acting insulin aspart, insulin aspart, type 1 diabetes, pharmacokinetics, pharmacodynamics, euglycaemic clamp, glucose-lowering effect, subcutaneous insulin, insulin formulations, glycemic control, postprandial blood glucose, insulin sensitivity, insulin clearance
- MeSH terms
- Adult, Diabetes Mellitus, Type 1, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Injections, Subcutaneous, Male, Randomized Controlled Trials as Topic, Cross-Over Studies, Insulin Aspart
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