Pharmacokinetics and pharmacodynamics of insulin glargine given in the evening as compared with in the morning in type 2 diabetes
Abstract
Objective To compare pharmacokinetics (PK) and pharmacodynamics (PD) of insulin glargine in type 2 diabetes mellitus (T2DM) after evening versus morning administration. Research design and methods Ten T2DM insulin-treated persons were studied during 24-h euglycemic glucose clamp, after glargine injection (0.4 units/kg s.c.), either in the evening (2200 h) or the morning (1000 h). Results The 24-h glucose infusion rate area under the curve (AUC0-24h) was similar in the evening and morning studies (1,058 ± 571 and 995 ± 691 mg/kg × 24 h, P = 0.503), but the first 12 h (AUC0-12h) was lower with evening versus morning glargine (357 ± 244 vs. 593 ± 374 mg/kg × 12 h, P = 0.004), whereas the opposite occurred for the second 12 h (AUC12-24h 700 ± 396 vs. 403 ± 343 mg/kg × 24 h, P = 0.002). The glucose infusion rate differences were totally accounted for by different rates of endogenous glucose production, not utilization. Plasma insulin and C-peptide levels did not differ in evening versus morning studies. Plasma glucagon levels (AUC0-24h 1,533 ± 656 vs. 1,120 ± 344 ng/L/h, P = 0.027) and lipolysis (free fatty acid AUC0-24h 7.5 ± 1.6 vs. 8.9 ± 1.9 mmol/L/h, P = 0.005; β-OH-butyrate AUC0-24h 6.8 ± 4.7 vs. 17.0 ± 11.9 mmol/L/h, P = 0.005; glycerol, P Conclusions The PD of insulin glargine differs depending on time of administration. With morning administration insulin activity is greater in the first 0-12 h, while with evening administration the activity is greater in the 12-24 h perio…
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The principal action of basal insulin is to restrain hepatic glucose production and limit hyperglycemia overnight and between meals.
“The principal action of basal insulin is to restrain hepatic glucose production and limit hyperglycemia overnight and between meals (164,165).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [164]
Cites
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“(19) described a robust and well-defined rhythm in insulin sensitivity in T2DM patients, with lower sensitivity in themorning and higher sensitivity in the evening.”
BackgroundResultInfluentialMeneghini, L., Atkin, S. L., Gough, S. C. L., Raz, I., Blonde, L., Shestakova, M., Bain, S., Johansen, T., Begtrup, K., Birkeland, K. I., et al. (2013) · Diabetes Care · doi:10.2337/dc12-1668 · Cited by 226 · see citing works
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9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2022</i>
American Diabetes Association Professional Practice Committee (2022) · Diabetes Care · doi:10.2337/dc22-s009 · Cited by 1,555 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2021</i>
American Diabetes Association (2021) · Diabetes Care · doi:10.2337/dc21-s009 · Cited by 972 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2020</i>
American Diabetes Association (2020) · Diabetes Care · doi:10.2337/dc20-s009 · Cited by 914 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Care in Diabetes—2023</i>
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s009 · Cited by 851 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2019</i>
American Diabetes Association (2019) · Diabetes Care · doi:10.2337/dc19-s009 · Cited by 739 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Bajaj, M., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s009 · Cited by 728 · see citing works
Doyle-Delgado, K., Chamberlain, J. J., Shubrook, J. H., Skolnik, N., & Trujillo, J. (2020) · Annals of Internal Medicine · doi:10.7326/m20-2470 · Cited by 111 · see citing works
- Authors
- Porcellati, F., Lucidi, P., Cioli, P., Candeloro, P., Marinelli Andreoli, A., Marzotti, S., Ambrogi, M., Bolli, G. B., & Fanelli, C. G.
- Affiliations
- University of Perugia (IT)
- Department of Medicine, University of Perugia Medical School, Perugia, Italy
- Corresponding author
- Bolli, Geremia B.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2014-12-18
- Volume
- 38
- Issue
- 3
- Pages
- 503-512
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2146550252
- Cited by
- 52
- References
- 5
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 6 · 2022: 2 · 2021: 3 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 3
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (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 › Surgery › Pancreatic function and diabetes
- Keywords
- insulin glargine, type 2 diabetes, pharmacokinetics, pharmacodynamics, glucose infusion rate, endogenous glucose production, glucagon, lipolysis, free fatty acids, beta-hydroxybutyrate, glycerol, C-peptide, plasma insulin, hyperinsulinemic-euglycemic clamp, basal insulin
- MeSH terms
- Insulin Glargine, Aged, Blood Glucose, C-Peptide, Circadian Rhythm, Diabetes Mellitus, Type 2, Drug Administration Schedule, Fatty Acids, Nonesterified, Female, Glucose, Humans, Hypoglycemic Agents, Injections, Insulin Resistance, Male, Middle Aged, Glucose Clamp Technique, Cross-Over Studies, Insulin, Long-Acting
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