Dose-response effects of insulin glargine in type 2 diabetes
Open accessAbstract
OBJECTIVE: To determine the pharmacokinetic and pharmacodynamic dose-response effects of insulin glargine administered subcutaneously in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Twenty obese type 2 diabetic individuals (10 male and 10 female, aged 50 ± 3 years, with BMI 36 ± 2 kg/m2 and A1C 8.3 ± 0.6%) were studied in this single-center, placebo-controlled, randomized, double-blind study. Five subcutaneous doses of insulin glargine (0, 0.5, 1.0, 1.5, and 2.0 units/kg) were investigated on separate occasions using the 24-h euglycemic clamp technique. RESULTS: Glargine duration of action to reduce glucose, nonessential fatty acid (NEFA), and β-hydroxybutyrate levels was close to or >24 h for all four doses. Increases in glucose flux revealed no discernible peak and were modest with maximal glucose infusion rates of 9.4, 6.6, 5.5, and 2.8 μmol/kg/min for the 2.0, 1.5, 1.0, and 0.5 units/kg doses, respectively. Glargine exhibited a relatively hepatospecific action with greater suppression (P < 0.05) of endogenous glucose production (EGP) compared with little or no increases in glucose disposal. CONCLUSION: A single subcutaneous injection of glargine at a dose of ≥0.5 units/kg can acutely reduce glucose, NEFA, and ketone body levels for 24 h in obese insulin-resistant type 2 diabetic individuals. Glargine lowers blood glucose by mainly inhibiting EGP with limited effects on stimulating glucose disposal. Large doses of glargine have minimal effects on glucose flux and retain a relatively hepatospecific action in type 2 diabetes.
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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 [165]
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- Authors
- Wang, Z., Hedrington, M. S., Gogitidze Joy, N., Briscoe, V. J., Richardson, M. A., Younk, L., Nicholson, W., Tate, D. B., & Davis, S. N.
- Affiliations
- Vanderbilt University (US)
- University of Maryland, Baltimore (US)
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
- Corresponding author
- Davis, Stephen N.
- ORCID
- Davis, Stephen N.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2010-03-31
- Volume
- 33
- Issue
- 7
- Pages
- 1555-1560
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC2890358
- OpenAlex
- W2155918752
- Cited by
- 44
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 3 · 2014: 6 · 2012: 4
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- 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)
- Funders
- Vanderbilt University
- National Institutes of Health (5p60dk020593-31, DK-020593)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK020593, P30DK079637)
- National Center for Research Resources (M01RR000095)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin glargine, type 2 diabetes, dose-response relationship, pharmacokinetics, pharmacodynamics, duration of action, euglycemic clamp, endogenous glucose production, glucose disposal, beta-hydroxybutyrate, ketone bodies, insulin resistance, obesity, subcutaneous insulin
- MeSH terms
- Insulin Glargine, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Fatty Acids, Nonesterified, Female, Glucagon, Humans, Hypoglycemic Agents, Injections, Subcutaneous, Insulin, Male, Middle Aged, Glucose Clamp Technique, Insulin, Long-Acting
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