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Cited by 126Diabetes Treatment and ManagementChronic Kidney Disease and DiabetesAcute Kidney Injury Research

Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial

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Tonneijck, Lennart, Smits, Mark M., Muskiet, Marcel H. A., Hoekstra, Trynke, Kramer, Mark H. H., Danser, A. H. Jan, Diamant, Michaela, Joles, Jaap A. +1 more·2016·Diabetologia
DOI 10.1007/s00125-016-3938-zPMC PMC4901099
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Abstract

AIMS/HYPOTHESIS: This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients. METHODS: We included overweight (BMI 25-40 kg/m(2)) men and postmenopausal women, aged 35-75 years with type 2 diabetes (HbA1c 48-75 mmol/mol; 6.5-9.0%) and estimated GFR ≥ 60 ml min(-1) 1.73 m(-2). Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (PGLO) and vascular resistance of the afferent (RA) and efferent (RE) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FENa), potassium (FEK) and urea (FEU), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined. RESULTS: Of the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide (n = 24) did not affect GFR (mean difference +2 ± 3 ml min(-1) 1.73 m(-2), p = 0.489), ERPF, FF, ERVR or PGLO, compared with placebo (n = 28). Exenatide increased RA (p < 0.05), but did not change RE. Exenatide increased FENa, FEK, urine osmolality and pH, while FEU, urinary flow and free water clearance were decreased (all p < 0.05). Osmolar clearance and renal damage makers were not affected. Diastolic BP and mean arterial pressure increased by 3 ± 1 and 6 ± 2 mmHg, respectively, whereas plasma glucose decreased by 1.4 ± 0.1 mmol/l (all p < 0.05). CONCLUSIONS/INTERPRETATION: Exenatide infusion does not acutely affect renal haemodynamics in overweight type 2 diabetes patients at normal filtration levels. Furthermore, acute GLP-1RA administration increases proximal sodium excretion in these patients. TRIAL REGISTRATION: ClincialTrials.gov NCT01744236 FUNDING : The research leading to these results has been funded from: (1) the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement number 282521 - the SAFEGUARD project; and (2) the Dutch Kidney Foundation, under grant agreement IP12.87.

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  • In infusion studies with exenatide, measured GFR was increased in healthy volunteers and unchanged in people with type 2 diabetes.

    “however, in other infusion studies with the GLP-1 receptor agonist exenatide, measured GFR (mGFR) was increased in healthy volunteers (26) and unchanged in people with T2D (30).”

    From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [30]

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Authors
Tonneijck, L., Smits, M. M., Muskiet, M. H. A., Hoekstra, T., Kramer, M. H. H., Danser, A. H. J., Diamant, M., Joles, J. A., & van Raalte, D. H.
Affiliations
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Amsterdam Public Health (NL)
  • Erasmus MC (NL)
  • University Medical Center Utrecht (NL)
Corresponding author
Tonneijck, Lennart
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2016-04-01
Volume
59
Issue
7
Pages
1412-1421
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-016-3938-z
PMC
PMC4901099
OpenAlex
W2315065708
Cited by
126
References
46
Citations by year
2026: 7 · 2025: 14 · 2024: 10 · 2023: 10 · 2022: 9 · 2021: 15 · 2020: 13 · 2019: 20 · 2018: 14 · 2017: 10 · 2016: 4
FWCI
16.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetologia (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
  • VU Research Portal (publishedVersion, other-oa)
  • Pure Amsterdam UMC (submittedVersion, cc-by)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • RePub (Erasmus University Rotterdam) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • AstraZeneca
  • Sanofi
  • Vanderbilt University Medical Center
  • European Commission (282521)
  • Nierstichting (IP12.87, grant agreement IP12.87)
  • Novo Nordisk
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
exenatide, GLP-1 receptor agonists, type 2 diabetes, renal function, glomerular filtration rate, effective renal plasma flow, renal hemodynamics, tubular function, sodium excretion, potassium excretion, urea excretion, free water clearance, renal damage markers, overweight patients, postmenopausal women
MeSH terms
Glucagon-Like Peptide-1 Receptor, Exenatide, Adult, Aged, Blood Pressure, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glomerular Filtration Rate, Hemodynamics, Humans, Hypoglycemic Agents, Kidney, Male, Middle Aged, Peptides, Venoms, Placebo Effect, Overweight

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