Severe acute renal failure in patients treated with glucagon-like peptide-1 receptor agonists

Dubois-Laforgue, D.; Boutboul, David; Lévy, Dominique; Joly, Dominique; Timsit, José

doi:10.1016/j.diabres.2013.11.014

Cited by 22 publications

(13 citation statements)

References 9 publications

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“…1 There also have been some reports of acute pancreatitis 1 and renal failure. 3 Analysis of experimental data indicates that exenatide is able to induce pancreatic damage in mice. 4 Only 1 report analyzed the immunologic effects of exenatide.…”

Section: To the Editormentioning

confidence: 98%

A case report of allergy to exenatide

Perez¹,

Martinez-Tadeo²,

Callero³

et al. 2014

The Journal of Allergy and Clinical Immunology: In Practice

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Section: To the Editormentioning

confidence: 98%

A case report of allergy to exenatide

Perez¹,

Martinez-Tadeo²,

Callero³

et al. 2014

The Journal of Allergy and Clinical Immunology: In Practice

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“…Exenatide has been associated with the development of acute kidney injury in about 100 case reports [140][141][142][143][144][145][146]. In most reports, acute kidney injury was attributed to pre-renal acute failure due to exenatide-induced nausea and vomiting, decreased fluid intake, and significant loss of fluids.…”

Section: Renal Effectsmentioning

confidence: 99%

Adverse Effects of GLP-1 Receptor Agonists

2014

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■ AbstractGlucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists.

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“…Published case reports have documented the relationship between exenatide [116][117][118][119][120][121] or liraglutide [121][122][123] use and acute kidney injury in patients with T2DM. Both acute interstitial nephritis and acute tubular necrosis may account for GLP-1 receptor agonist-related acute renal failure [121].…”

Section: Discussionmentioning

confidence: 96%

“…Both acute interstitial nephritis and acute tubular necrosis may account for GLP-1 receptor agonist-related acute renal failure [121]. One of the proposed explanations was the occurrence of gastrointestinal side effects with recurrent vomiting leading to dehydration and secondary acute kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes

Scheen

2014

Clin Pharmacokinet

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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 eliminated by the kidney, but it should be used with caution because of the limited experience in patients with CKD. Only limited pharmacokinetic data are also available for lixisenatide, exenatide long-acting release (LAR) and other once-weekly GLP-1 receptor agonists in current development. Several case reports of acute renal failure have been described with GLP-1 receptor agonists, probably triggered by dehydration resulting from gastrointestinal adverse events. However, increasing GLP-1 may also exert favourable renal effects that could contribute to reducing the risk of diabetic nephropathy. In conclusion, the already large reassuring experience with DPP-4 inhibitors in patients with CKD offers new opportunities to the clinician, whereas more caution is required with GLP-1 receptor agonists because of the limited experience in this population.

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Severe acute renal failure in patients treated with glucagon-like peptide-1 receptor agonists

Cited by 22 publications

References 9 publications

A case report of allergy to exenatide

A case report of allergy to exenatide

Adverse Effects of GLP-1 Receptor Agonists

Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes

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