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Cited by 125Diabetes Management and ResearchDiabetes Treatment and ManagementPancreatic function and diabetes

Pharmacokinetics and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects

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de la Peña, Amparo, Riddle, Matthew, Morrow, Linda A., Jiang, Honghua H., Linnebjerg, Helle, Scott, Adam, Win, Khin M., Hompesch, Marcus +3 more·2011·Diabetes Care
DOI 10.2337/dc11-0721PMC PMC3220843
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Abstract

OBJECTIVE: Human regular U-500 (U-500R) insulin (500 units/mL) is increasingly being used clinically, yet its pharmacokinetics (PK) and pharmacodynamics (PD) have not been well studied. Therefore, we compared PK and PD of clinically relevant doses of U-500R with the same doses of human regular U-100 (U-100R) insulin (100 units/mL). RESEARCH DESIGN AND METHODS: This was a single-site, randomized, double-blind, crossover euglycemic clamp study. Single subcutaneous injections of 50- and 100-unit doses of U-500R and U-100R were administered to 24 healthy obese subjects. RESULTS: Both overall insulin exposure (area under the serum insulin concentration versus time curve from zero to return to baseline [AUC(0-)(t)(')]) and overall effect (total glucose infused during a clamp) were similar between formulations at both 50- and 100-unit doses (90% [CI] of ratios contained within [0.80, 1.25]). However, peak concentration and effect were significantly lower for U-500R at both doses (P < 0.05). Both formulations produced relatively long durations of action (18.3 to 21.5 h). Time-to-peak concentration and time to maximum effect were significantly longer for U-500R than U-100R at the 100-unit dose (P < 0.05). Time variables reflective of duration of action (late tR(max50), tR(last)) were prolonged for U-500R versus U-100R at both doses (P < 0.05). CONCLUSIONS: Overall exposure to and action of U-500R insulin after subcutaneous injection were no different from those of U-100R insulin. For U-500R, peaks of concentration and action profiles were blunted and the effect after the peak was prolonged. These findings may help guide therapy with U-500R insulin for highly insulin-resistant patients with diabetes.

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  • U-500 regular insulin has similar onset but a delayed, blunted, and prolonged peak effect and longer duration of action compared with U-100 regular insulin.

    “U-500 regular insulin has distinct pharmacokinetics with similar onset but a delayed, blunted, and prolonged peak effect and longer duration of action compared with U-100 regular insulin; thus, it has characteristics more like a premixed intermediate-acting (NPH) and regular insulin product and can be used as two or three daily injections (177,178).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [177]

    The Results report similar onset, lower peak effect, and prolonged duration for U-500R versus U-100R. However, the Abstract Results and Conclusions specify that time to maximum effect was significantly delayed only at the 100-unit dose; the claim presents that delay without the dose qualification. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • U-500 regular insulin has characteristics more like a premixed intermediate-acting (NPH) and regular insulin product.

    “U-500 regular insulin has distinct pharmacokinetics with similar onset but a delayed, blunted, and prolonged peak effect and longer duration of action compared with U-100 regular insulin; thus, it has characteristics more like a premixed intermediate-acting (NPH) and regular insulin product and can be used as two or three daily injections (177,178).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [177]

    The Conclusions (page unavailable) report a similar onset to U-100 regular insulin and a longer duration of action, which the authors say may permit multiple daily injections without basal insulin. Those findings support the short- and longer-acting aspects of the analogy, but the paper does not compare U-500 with an NPH/regular premix or state that their characteristics are alike. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 19

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Authors
de la Peña, A., Riddle, M., Morrow, L. A., Jiang, H. H., Linnebjerg, H., Scott, A., Win, K. M., Hompesch, M., Mace, K. F., Jacobson, J. G., & Jackson, J. A.
Affiliations
  • Eli Lilly and Company, Indianapolis, Indiana
  • Oregon Health & Science University (US)
  • Profil Institute for Clinical Research (US)
  • Eli Lilly (United States) (US)
  • Eli Lilly (United Kingdom) (GB)
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2011-11-14
Volume
34
Issue
12
Pages
2496-2501
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc11-0721
PMC
PMC3220843
OpenAlex
W2079259745
Cited by
125
References
0
Citations by year
2026: 2 · 2025: 8 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 11 · 2020: 10 · 2019: 4 · 2018: 8 · 2017: 11 · 2016: 16 · 2015: 15 · 2014: 13 · 2013: 10 · 2012: 5
FWCI
7.35
Type
journal article
Language
en
Update notices
correction (2014-08-01)
Open access
Licence
Locations
  • Diabetes Care (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
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 › Surgery › Pancreatic function and diabetes
Keywords
U-500 insulin, U-100 insulin, insulin pharmacokinetics, insulin pharmacodynamics, high-dose insulin, insulin duration of action, insulin resistance, obesity, euglycemic clamp, subcutaneous insulin injection, diabetes treatment
MeSH terms
Adult, Aged, Blood Glucose, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Obesity, Glucose Clamp Technique, Cross-Over Studies, Area Under Curve, Insulin, Regular, Human

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