Exenatide and renal failure

Ferrer-García, Juan Carlos; Martinez-Chanza, N.; Tolosa-Torréns, Mercedes; Sánchez-Juan, Carlos

doi:10.1111/j.1464-5491.2010.03009.x

Cited by 24 publications

(13 citation statements)

References 4 publications

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“…Events of exenatide-associated renal impairment or renal failure are reported infrequently in published studies 56,57. In the current analysis, the exposure-adjusted incidence rate of renal impairment was 1.6 per 100 PY in both the exenatide and pooled comparator groups.…”

Section: Discussionmentioning

confidence: 43%

Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials

MacConell¹,

Brown²,

Gurney³

et al. 2012

DMSO

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BackgroundExenatide twice daily is a first-in-class glucagon-like peptide receptor agonist approved for the treatment of type 2 diabetes. The objective of this analysis was to evaluate the safety profile of exenatide twice daily and to compare its profile with that of a pooled comparator (placebo and insulin) in patients with type 2 diabetes.MethodsData from 19 completed, randomized, controlled clinical trials of exenatide twice daily (5 μg and 10 μg) were pooled and analyzed; the pooled data included 5594 intent-to-treat patients who were followed for 12–52 weeks. Incidence rates, exposure-adjusted incidence rates, and 95% confidence intervals around risk differences between groups were calculated.ResultsBaseline demographics and exposure time were comparable between groups (exenatide, N = 3261; pooled comparator, N = 2333; mean exposure time 166–171 days). Transient, mild- to-moderate nausea was the most frequent adverse event with exenatide (36.9% versus 8.3% in the pooled comparator). The incidence of hypoglycemia (minor or major) with concomitant sulfonylurea (exenatide 26.5%, pooled comparator 20.7%) was higher than that without sulfonylurea (exenatide 3.1%, pooled comparator 2.7%) in all groups. Serious adverse events, discontinuations due to serious adverse events, and deaths were reported with similar frequency in the exenatide and pooled comparator groups. Composite exposure-adjusted incidence rates were not statistically different between groups for pancreatitis, renal impairment, or major adverse cardiac events; there was a difference in incidence rates for benign thyroid neoplasm (0.3% versus 0%).ConclusionOverall, this analysis, representing over 1500 patient-years of exposure, demonstrated that exenatide twice daily was safe and generally well tolerated in patients with type 2 diabetes. The incidence of most adverse events, including serious adverse events, was similar in both exenatide-treated and comparator-treated patients. The most distinct differences between groups were in gastrointestinal-related adverse events, which is consistent with other therapies within the glucagon-like peptide class.

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Section: Discussionmentioning

confidence: 43%

Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials

MacConell¹,

Brown²,

Gurney³

et al. 2012

DMSO

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“…48,49 While a recently published retrospective cohort study of a claims database did not reveal an association between the use of exenatide and acute renal failure, 53 case reports of altered kidney function associated with exenatide use have been discussed in several other publications. [54][55][56][57] Exenatide Long-Acting Release Exenatide is also available in a long-acting release (LAR) formulation, which only needs to be injected once per week. This formulation, which was recently approved (by the European Union in 2011 and by the United States in 2012), appears to be more effective at improving glycemic control than the twice-daily formulation.…”

Section: Prescribing Informationmentioning

confidence: 99%

Incretin Therapies in the Management of Patients with Type 2 Diabetes Mellitus and Renal Impairment

Dejager

Schweizer

2012

Hospital Practice

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Renal impairment (RI) is common among patients with type 2 diabetes mellitus (T2DM), and these patients also experience an age-related decline in renal function. At the same time, treatment options are more limited and treatment is more complex, particularly in patients with moderate or severe RI due to contraindications, need for dose adjustment and/or regular monitoring, and side effects, such as fluid retention and hypoglycemia, which are a more serious concern in this patient population. Incretin therapies, consisting of the injectable glucagon-like peptide-1 (GLP-1) receptor agonists and the oral dipeptidyl peptidase-4 (DPP-4) inhibitors, are a promising new class of antihyperglycemic drugs. In the overall population, they improve glycemic control in a glucose-dependent manner and are not likely to cause hypoglycemia, representing a clear advantage in at-risk populations. Data regarding use of these agents in renally impaired patients have started to emerge, and the objective of this article is to provide an overview of the currently available data and the potential role of these novel agents in the management of patients with T2DM and RI. Data for the GLP-1 receptor agonists in patients with moderate or severe RI are still limited, with no trials dedicated to these populations currently published. In addition, their potential to cause gastrointestinal side effects may limit use in patients with RI due to the risk of dehydration and hypovolemia. The use of GLP-1 receptor agonists in patients with moderate or severe RI is therefore, at present, underlying caution and/or restrictions. On the other hand, data from specific trials in patients with moderate or severe RI are now becoming available for most of the DPP-4 inhibitors. These studies demonstrate good efficacy and tolerability of the DPP-4 inhibitors in patients with moderate or severe RI, thus opening a place for these therapies in the treatment of populations with T2DM and RI. Several of the DPP-4 inhibitors are already approved for use in patients with moderate or severe RI, including for those with end-stage renal disease. While discussing the advantages related to their common mechanism of action, this article also describes differences among the DPP-4 inhibitors (eg, related to their pharmacokinetic properties and the available clinical data). In conclusion, while initial data for these new therapies are promising, further experience is needed to fully assess the risk-benefit balance and clinical positioning of these agents in RI populations.

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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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Exenatide and renal failure

Cited by 24 publications

References 4 publications

Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials

Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials

Incretin Therapies in the Management of Patients with Type 2 Diabetes Mellitus and Renal Impairment

Adverse Effects of GLP-1 Receptor Agonists

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