Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects
Abstract
We have previously shown that type 2 diabetic patients have decreased plasma concentrations of glucagon-like peptide 1 (GLP-1) compared with healthy subjects after ingestion of a standard mixed meal. This decrease could be caused by differences in the metabolism of GLP-1. The objective of this study was to examine the pharmacokinetics of GLP-1 in healthy subjects and type 2 diabetic patients after iv bolus doses ranging from 2.5-25 nmol/subject. Bolus injections iv of 2.5, 5, 15, and 25 nmol of GLP-1 and a meal test were performed in six type 2 diabetic patients [age, mean (range): 56 (48-67) yr; body mass index: 31.2 (27.0-37.7) kg/m(2); fasting plasma glucose: 11.9 (8.3-14.3) mmol/liter; hemoglobin A(1C): 9.6 (7.0-12.5)%]. For comparison, six matched healthy subjects were examined. Peak plasma GLP-1 concentrations increased linearly with increasing doses of GLP-1 and were similar for type 2 diabetic patients and healthy subjects. The peak concentrations of total GLP-1 (C-terminal) after 2.5, 5, 15, and 25 nmol of GLP-1 were 357 +/- 56, 647 +/- 141, 1978 +/- 276, 3435 +/- 331 pmol/liter in the type 2 diabetic patients and 315 +/- 37, 676 +/- 64, 1848 +/- 146, 3168 +/- 358 pmol/liter, respectively, in the healthy subjects (not statistically significant). Peak concentrations of the intact GLP-1 peptide (N-terminal) were: 69 +/- 17, 156 +/- 44, 703 +/- 77, and 1070 +/- 117 pmol/liter in the type 2 diabetic patients and 75 +/- 14, 160 +/- 40, 664 +/- 79, 974 +/- 87 in the healthy subjects (not statistically significant). GLP-1 was eliminated rapidly with clearances of intact GLP-1 after 2.5, 5, 15, and 25 nmol of GLP-1 amounting to: 9.0 +/- 5.0, 8.1 +/- 6.0, 4.0 +/- 1.0, 4.0 +/- 1.0 liter/min in type 2 diabetic patients and 8.4 +/- 4.2, 7.6 +/- 4.5, 5.0 +/- 2.0, 5.0 +/- 1.0 liter/min in healthy subjects. The volume of distribution ranged from 9-26 liters per subject. No significant differences were found between healthy subjects and type 2 diabetic subjects. We conclude that elimination of GLP-1 is the same in obese type 2 diabetic patients and matched healthy subjects. The impaired incretin response seen after ingestion of a standard breakfast meal must therefore be caused by a decreased secretion of GLP-1 in type 2 diabetic patients.
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GLP-1 has a half-life of 1 to 2 minutes due to N-terminal degradation by DPP-4.
“The half-life of GLP-1 is 1 to 2 minutes due to N-terminal degradation by the enzyme dipeptidyl peptidase 4 (DPP-4).(8, 9)”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [8]
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- Authors
- Vilsbøll, T., Agersø, H., Krarup, T., & Holst, J. J.
- Affiliations
- University of Copenhagen (DK)
- Ferring Pharmaceuticals (Denmark) (DK)
- Gentofte Hospital (DK)
- Corresponding author
- Vilsbøll, T.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2003-01
- Volume
- 88
- Issue
- 1
- Pages
- 220-224
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2024409703
- Cited by
- 444
- References
- 21
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 16 · 2023: 13 · 2022: 13 · 2021: 13 · 2020: 5 · 2019: 17 · 2018: 10 · 2017: 16 · 2016: 25 · 2015: 23 · 2014: 22 · 2013: 28 · 2012: 29
- FWCI
- 10.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Gentofte Hospital
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- glucagon-like peptide-1, pharmacokinetics, type 2 diabetes, obesity, elimination rate, intravenous bolus, dose proportionality, healthy subjects comparison, test meal, GLP-1 receptor agonists, GLP-1 analogues, GLP-1 receptor antagonists, GLP-1 receptor signaling
- MeSH terms
- Aged, Diabetes Mellitus, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Female, Glucagon, Humans, Injections, Intravenous, Male, Middle Aged, Obesity, Osmolar Concentration, Peptide Fragments, Protein Precursors, Reference Values, Glucagon-Like Peptide 1
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