Glucagon-Like Peptide-1 (GLP-1): Effect on Kidney Hemodynamics and Renin-Angiotensin-Aldosterone System in Healthy Men
Abstract
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) is an incretin hormone with multiple actions in addition to control of glucose homeostasis. GLP-1 is known to cause natriuresis in humans, but the effects on basic renal physiology are still partly unknown. SUBJECTS AND METHODS: Twelve healthy young males were examined in a randomized, controlled, double-blinded, single-day, crossover trial to evaluate the effects of 2 hours GLP-1 infusion on kidney functions. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed with (51)Cr-EDTA and (123)I-hippuran, respectively, using a constant infusion renal clearance technique based on timed urine sampling. RESULTS: GLP-1 had no significant effect on either GFR [+1.9%, 95% confidence interval (-0.8; 4.6%)] or RPF [+2.4%, 95% confidence interval (-3.6; 8.8%)]. Fractional urine excretion of lithium increased 9% (P = .013) and renal sodium clearance increased 40% (P = .007). Angiotensin II decreased 19% (P = .003), whereas renin, aldosterone, and the urinary excretion of angiotensinogen showed no significant changes. glp-1 did not affect blood pressure but induced a small transient increase in heart rate. CONCLUSION: The results indicate that although GLP-1 markedly reduces proximal tubule sodium reabsorption, the acute effects on GFR and RPF are very limited in healthy humans. The finding of GLP-1's ability to reduce angiotensin II concentration is novel and should be further elucidated.
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Increased urinary sodium excretion and increased urine volume induced by GLP-1 peptide and its receptor agonists have been confirmed in rodents, healthy volunteers, insulin-resistant obese males, and patients with type 2 diabetes during acute infusion studies.
“Indeed, increased urinary sodium excretion and increased urine volume induced by GLP-1 peptide and its receptor agonists have been confirmed in rodents (25), healthy volunteers (26, 27), insulin-resistant obese males (28, 29), and patients with T2D during acute infusion studies (30).”
From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [27]
The Results in “Water, electrolyte, and lithium handling” report a 40% increase in sodium clearance during acute GLP-1 infusion in healthy men. They also state that urine flow increased insignificantly, so this study does not confirm increased urine volume in healthy volunteers. The other populations in the citing sentence have separate citations and are not attributed to this source. (LLM, conf=0.91)
Experimental — accuracy not yet measuredGLP-1 and GLP-1RAs lower circulating angiotensin II levels by approximately 20% in clinical studies.
“The natriuretic effect of GLP-1RAs may also be partially attributed to a reduction of the activity of the renin–angiotensin–aldosterone system, as in clinical studies, GLP-1 and GLP-1RAs have been found to lower circulating angiotensin II levels by approximately 20% [24, 25].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [24]
The natriuretic effect of GLP-1RAs may be partially attributed to a reduction of renin-angiotensin-aldosterone system activity.
“The natriuretic effect of GLP-1RAs may also be partially attributed to a reduction of the activity of the renin–angiotensin–aldosterone system, as in clinical studies, GLP-1 and GLP-1RAs have been found to lower circulating angiotensin II levels by approximately 20% [24, 25].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [24]
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- Authors
- Skov, J., Dejgaard, A., Frøkiær, J., Holst, J. J., Jonassen, T., Rittig, S., & Christiansen, J. S.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- Aarhus University (DK)
- Novo Nordisk Foundation Center for Basic Metabolic Research (DK)
- University of Copenhagen (DK)
- Aarhus University Hospital (DK)
- Department of Endocrinology and Internal Medicine (J.S., J.S.C.), DK-8000 Aarhus, Denmark
- Corresponding author
- Skov, Jeppe
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2013-04-01
- Volume
- 98
- Issue
- 4
- Pages
- E664-E671
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2047793705
- Cited by
- 228
- References
- 36
- Citations by year
- 2026: 22 · 2025: 29 · 2024: 22 · 2023: 9 · 2022: 18 · 2021: 16 · 2020: 21 · 2019: 17 · 2018: 12 · 2017: 15 · 2016: 16 · 2015: 15 · 2014: 12 · 2013: 4
- FWCI
- 10.66
- 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
- Aarhus Universitet
- Aarhus Universitetshospital
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- glucagon-like peptide-1, renal hemodynamics, glomerular filtration rate, renal plasma flow, renin-angiotensin-aldosterone system, angiotensin II, sodium excretion, proximal tubule sodium reabsorption, incretins, healthy men
- MeSH terms
- Adult, Double-Blind Method, Glomerular Filtration Rate, Health, Hemodynamics, Humans, Kidney, Male, Placebos, Regional Blood Flow, Renin-Angiotensin System, Urinalysis, Cross-Over Studies, Glucagon-Like Peptide 1, Young Adult
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