Potential Linagliptin-Induced Renal Impairment

Kutoh, None

doi:10.4021/jmc807w

Cited by 3 publications

(4 citation statements)

References 7 publications

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“…Although there have been isolated case reports of renal toxicity after initiation of DPP‐4 inhibitors , an increased risk has not been confirmed in large managed care and pooled trial database analyses of people given appropriate recommended doses . In addition, there is no clear safety signal from the long‐term efficacy studies in people with renal impairment as summarized in Table , but also from the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR TIMI 53) and Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trials, the two recently reported large‐scale cardiovascular safety studies of DPP‐4 inhibitor therapy that both included significant proportions of people with renal impairment [16% with estimated glomerular filtration rate (eGFR) ≤50 ml/min/1.73 m 2 in SAVOR TIMI 53, and 29% with eGFR <60 ml/min/1.73 m 2 in EXAMINE].…”

Section: Tolerability and Safetymentioning

confidence: 99%

“…Although there have been isolated case reports of renal toxicity after initiation of DPP-4 inhibitors [40][41][42], an increased risk has not been confirmed in large managed care and pooled trial database analyses of people given appropriate recommended doses [43,44]. In addition, there is no clear safety signal from the long-term efficacy studies in people with renal impairment as summarized in Table 3 In SAVOR TIMI 53, people were excluded if they had ESRD and were undergoing long-term dialysis, had undergone a renal transplantation or had a serum creatinine >530 μmol/l [4].…”

Section: Renal Toxicitymentioning

confidence: 99%

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Dipeptidyl peptidase‐4 inhibitors: pharmacokinetics, efficacy, tolerability and safety in renal impairment

Davis

2014

Diabetes Obesity Metabolism

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The dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of blood glucose-lowering therapy with proven efficacy, tolerability and safety. Four of the five commercially available DPP-4 inhibitors are subject to significant renal clearance, and pharmacokinetic studies in people with renal impairment have led to lower recommended doses based on creatinine clearance in order to prevent drug accumulation. Data from these pharmacokinetic studies and from supratherapeutic doses in healthy individuals and people with uncomplicated diabetes during development suggest, however, that there is a wide therapeutic margin. This should protect against toxicity if people with renal impairment are inadvertently prescribed higher doses than recommended. Doses appropriate to renal function are associated with reductions in HbA1c that are equivalent to those observed in people with type 2 diabetes who do not have renal impairment. Recent large-scale cardiovascular safety trials of saxagliptin and alogliptin have identified heart failure as a potential concern and renal impairment may increase the risk of this complication. Although the incidence of pancreatitis does not appear to be significantly increased by DPP-4 inhibitor therapy, renal impairment is also an independent risk factor. Additional data from other ongoing DPP-4 inhibitor cardiovascular safety trials should provide a more precise assessment of the risks of these uncommon complications, including in people with renal impairment.

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Section: Tolerability and Safetymentioning

confidence: 99%

Section: Renal Toxicitymentioning

confidence: 99%

Dipeptidyl peptidase‐4 inhibitors: pharmacokinetics, efficacy, tolerability and safety in renal impairment

Davis

2014

Diabetes Obesity Metabolism

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“…Moreover, our study classified the data in more detail by stratification according to age and sex. Some case reports have suggested that linagliptin can cause acute renal failure with hypotension and hyperkalemia when added to the treatment regimens of patients already receiving ACEIs 30,31 . Moreover, a recent in silico and in vivo study reported that many DPP-4Is, including linagliptin, could potentially inhibit ACE in concentrations close to those required for DPP-4 inhibition 32 .…”

Section: Discussionmentioning

confidence: 99%

Pharmacovigilance study of the association between dipeptidyl peptidase–4 inhibitors and angioedema using the FDA Adverse Event Reporting System (FAERS)

Ohyama

Shindo

Takahashi

et al. 2022

Sci Rep

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Dipeptidyl peptidase-4 (DPP-4) plays a minor role in degrading vasoactive peptides that cause angioedema when angiotensin-converting enzyme (ACE) is present and fully functional. This study investigated the association between DPP-4 inhibitors (DPP-4Is) and angioedema, including cases where the concomitant use of ACE inhibitors (ACEIs) was absent. We obtained data from the US Food and Drug Administration Adverse Event Reporting System and performed a disproportionality analysis, using the reporting odds ratio (ROR) and information component (IC) for signal detection in patients aged ≥ 40 years, stratified by age group and sex. No signal was detected for DPP-4Is when the entire dataset was analyzed. However, a signal was detected for the entire female subset group, the three stratified female groups aged ≥ 60 years, and males in their 40 s. After excluding the data of concomitant ACEI users, most ROR and IC values were lower and significant only for females in their 60 s and males aged ≥ 80 years. Regarding individual DPP-4Is signals, those detected for saxagliptin and sitagliptin in some age groups disappeared after excluding the data of ACEI users. Notably, linagliptin was the only DPP-4I where signals were detected in most female groups, regardless of age and without concomitant ACEI use. Our findings suggest that some DPP-4Is were associated with a higher reporting of angioedema as per age and sex, even in the absence of concomitant ACEI use.

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“…It may be prudent to exert caution when linagliptin is initiated in combination with ACE-inhibitors in patients with limited kidney reserve. Of note, a case of transient AKI associated with linagliptin use was reported in a patient with normal renal function who was also on ACE-inhibitor [ 7 ]. Therefore, we recommend to closely monitoring kidney function and blood pressure after linagliptin initiation in diabetic patients with advanced CKD also treated with ACE-inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Acute Kidney Injury Associated with Linagliptin

Nandikanti

Gosmanova

Gosmanov

2016

Case Reports in Endocrinology

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Linagliptin is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that is approved for the treatment of type 2 diabetes mellitus. About 5% of linagliptin is eliminated by the kidneys and no dose adjustment is recommended in kidney impairment. We report a first case of linagliptin-associated acute kidney injury (AKI) in a patient with preexisting chronic kidney disease (CKD). We hypothesize that AKI was due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use, which is known to impair autoregulation and potentiate hypotension-induced AKI. It may be prudent to exert caution and closely monitor kidney function when initiating linagliptin in combination with ACE-inhibitors in CKD patients.

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Potential Linagliptin-Induced Renal Impairment

Cited by 3 publications

References 7 publications

Dipeptidyl peptidase‐4 inhibitors: pharmacokinetics, efficacy, tolerability and safety in renal impairment

Dipeptidyl peptidase‐4 inhibitors: pharmacokinetics, efficacy, tolerability and safety in renal impairment

Pharmacovigilance study of the association between dipeptidyl peptidase–4 inhibitors and angioedema using the FDA Adverse Event Reporting System (FAERS)

Acute Kidney Injury Associated with Linagliptin

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