Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes
Abstract
The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic agents have limitations in patients with CKD, incretin-based therapies are increasingly used for the management of T2DM. This review analyses (1) the influence of CKD on the pharmacokinetics of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists; and (2) the efficacy/safety profile of these agents in clinical practice when prescribed in patients with both T2DM and CKD. Most DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin) are predominantly excreted by the kidneys. Thereby, pharmacokinetic studies showed that total exposure to the drug is increased in proportion to the decline of GFR, leading to recommendations for appropriate dose reductions according to the severity of CKD. In these conditions, clinical studies reported a good efficacy and safety profile in patients with CKD. In contrast, linagliptin is eliminated by a predominantly hepatobiliary route. As a pharmacokinetic study showed only minimal influence of decreased GFR on total exposure, no dose adjustment of linagliptin is required in the case of CKD. The experience with GLP-1 receptor agonists in patients with CKD is more limited. Exenatide is eliminated by renal mechanisms and should not be given in patients with severe CKD. Liraglutide is not eliminat…
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Lixisenatide and exenatide require the kidneys for elimination, result in higher exposure, and have limited data in individuals with eGFR <30 mL/min/1.73m2 or creatinine clearance <30 mL/min, respectively.
“Lixisenatide and exenatide, which require the kidneys for elimination, result in higher exposure to the medication and have limited data in individuals with eGFR <30 mL/min/1.73m 2 or creatinine clearance <30 mL/min, respectively (137-139).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [139]
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References 121 · Cited by 102
- Authors
- Scheen, A. J.
- Affiliations
- University of Liège (BE)
- Corresponding author
- Scheen, André J.
- ORCID
- Scheen, André J.
- Venue
- Clinical Pharmacokinetics
- Published
- 2014-10-21
- Volume
- 54
- Issue
- 1
- Pages
- 1-21
- ISSN
- 0312-5963 (ISSN-L)
- 1179-1926
- OpenAlex
- W2059897529
- Cited by
- 102
- References
- 121
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 2 · 2022: 10 · 2021: 6 · 2020: 9 · 2019: 6 · 2018: 16 · 2017: 17 · 2016: 21 · 2015: 8 · 2014: 2
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Clinical Pharmacokinetics (publishedVersion)
- PubMed (publishedVersion)
- ORBi (University of Liège) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- incretin-based therapy, chronic kidney disease, type 2 diabetes, DPP-4 inhibitors, GLP-1 receptor agonists, pharmacokinetics, dose adjustment, glomerular filtration rate, linagliptin, exenatide, liraglutide, lixisenatide, acute kidney injury, diabetic nephropathy, renal excretion, drug safety
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Receptors, Glucagon, Renal Insufficiency, Chronic, Incretins, Dipeptidyl-Peptidase IV Inhibitors
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