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Cited by 276Diabetes Management and ResearchDiabetes Treatment and ManagementPancreatic function and diabetes

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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

Mudaliar, S R, Lindberg, F A, Joyce, M, Beerdsen, P, Strange, P, Lin, A, Henry, R R·1999·Diabetes Care
DOI 10.2337/diacare.22.9.1501
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Abstract

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.

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Metadata

Authors
Mudaliar, S. R., Lindberg, F. A., Joyce, M., Beerdsen, P., Strange, P., Lin, A., & Henry, R. R.
Affiliations
University of California San Diego (US)
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
1999-09-01
Volume
22
Issue
9
Pages
1501-1506
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/diacare.22.9.1501
OpenAlex
W2150939399
Cited by
276
References
0
Citations by year
2026: 5 · 2025: 7 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 14 · 2020: 3 · 2019: 4 · 2018: 8 · 2017: 11 · 2016: 10 · 2015: 12 · 2014: 13 · 2013: 10 · 2012: 20
FWCI
6.10
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Center for Research Resources (MO1 RR00827, M01RR000827)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords
insulin aspart, regular insulin, insulin pharmacokinetics, insulin pharmacodynamics, subcutaneous injection site, deltoid muscle, thigh, glucose infusion rate, euglycemic clamp, C-peptide, insulin sensitivity, insulin clearance
MeSH terms
Absorption, Adult, Double-Blind Method, Humans, Hypoglycemic Agents, Injections, Intramuscular, Injections, Subcutaneous, Insulin, Male, Reference Values, Glucose Clamp Technique, Cross-Over Studies, Insulin Aspart

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