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Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro.
Open accessAbstract
To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1.5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.
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“The intermediate-acting NPH insulin provides good control of afternoon peaks of blood glucose caused by glucocorticoids.”
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“This approach might have an advantage over long-acting insulin because its effects show a similar timeline to that of glucocorticoid-induced afternoon peaks of hyperglycaemia.56 57”
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Heise, T., Nosek, L., Rønn, B. B., Endahl, L., Heinemann, L., Kapitza, C., & Draeger, E. (2004) · Diabetes · doi:10.2337/diabetes.53.6.1614 · Cited by 614
Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs
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Metadata
- Authors
- Lepore, M., Pampanelli, S., Fanelli, C., Porcellati, F., Bartocci, L., Di Vincenzo, A., Cordoni, C., Costa, E., Brunetti, P., & Bolli, G. B.
- Affiliations
- University of Perugia (IT)
- Department of Internal Medicine, University of Perugia, Italy.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-12-01
- Volume
- 49
- Issue
- 12
- Pages
- 2142-2148
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2158144637
- Cited by
- 818
- References
- 32
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 8 · 2023: 13 · 2022: 22 · 2021: 13 · 2020: 18 · 2019: 23 · 2018: 25 · 2017: 32 · 2016: 20 · 2015: 38 · 2014: 34 · 2013: 30 · 2012: 37
- FWCI
- 21.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- 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 › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- long-acting insulin, insulin glargine, NPH insulin, ultralente insulin, insulin lispro, insulin pump therapy, pharmacokinetics, pharmacodynamics, onset of action, duration of action, interindividual variability, type 1 diabetes, subcutaneous insulin injection, insulin analogues
- MeSH terms
- Insulin Glargine, Adult, Blood Glucose, Diabetes Mellitus, Type 1, Double-Blind Method, Humans, Hypoglycemic Agents, Injections, Subcutaneous, Insulin, Insulin, Isophane, Male, Osmolar Concentration, Cross-Over Studies, Insulin, Long-Acting, Insulin Lispro
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