Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin*

Graefe‐Mody, Ulrike; Friedrich, Christian; Port, Andreas; Ring, Arne; Retlich, Silke; Heise, Tim; Halabi, Atef; Woerle, HJ

doi:10.1111/j.1463-1326.2011.01458.x

Cited by 168 publications

(141 citation statements)

References 15 publications

(21 reference statements)

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“…Further, more patients who were prescribed linagliptin as first‐line treatment had baseline cardiac, renal and urinary disorders, an observation that was also reported in a previous post‐marketing surveillance study 31. Linagliptin is excreted via the biliary route rather than the renal route like other DPP‐4 inhibitors; therefore, it can be prescribed regardless of RI stage 32. Teneligliptin, which has the second highest rate of biliary excretion (34%),33 was also frequently prescribed in patients with RI stage G4+.…”

Section: Discussionmentioning

confidence: 99%

Persistence of oral antidiabetic treatment for type 2 diabetes characterized by drug class, patient characteristics and severity of renal impairment: A Japanese database analysis

Kadowaki

Sarai

Hirakawa

et al. 2018

Diabetes Obesity Metabolism

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AimTo evaluate the persistence with oral antidiabetic drug (OAD) treatment characterized by drug class, patient characteristics and severity of renal impairment (RI) in patients with type 2 diabetes (T2DM) in Japan.Materials and MethodsThis retrospective, observational study extracted data from a large‐scale hospital database (April 2008 to September 2016). Patients with T2DM aged ≥40 years on the day of their first prescription (index date) of any OAD (biguanides [BGs], thiazolidinediones [TZDs], sulphonylureas [SUs], glinides, dipeptidyl peptidase‐4 [DPP‐4] inhibitors, or α‐glucosidase inhibitors [α‐GIs]) available between January 1, 2014 and September 30, 2016 were identified. Sodium‐glucose co‐transporter‐2 inhibitors were not available at study initiation. Treatment persistence was assessed by Kaplan–Meier survival curves. Patients were also categorized by RI status using estimated glomerular filtration rate: ≥90 mL/min/1.73 m2 (G1); 60 to <90 mL/min/1.73 m2 (G2); 30 to <60 mL/min/1.73 m2 (G3); and <30 mL/min/1.73 m2 (G4+).ResultsWe identified 206 406 index dates from 162 116 eligible patients. The largest number of index dates (91634) was observed for DPP‐4 inhibitors, followed by BGs, SUs, α‐GIs, glinides and TZDs. Treatment persistence was longest for DPP‐4 inhibitors (median 17.0 months, 95% confidence interval [CI] 16.4‐17.5) and BGs (median 17.3 months, 95% CI 16.6‐18.2), and shortest for α‐GIs (median 5.6 months, 95% CI 5.4‐5.9) and SUs (median 4.3 months, 95% CI 4.2‐4.6). Persistence was longest with DPP‐4 inhibitors at all RI stages (G1–G4+), followed by BGs at stages G1/G2.ConclusionsThe longest OAD persistence was observed for BGs and DPP‐4 inhibitors at RI stages G1/G2, and for DPP‐4 inhibitors at RI stages G3/G4+.

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Section: Discussionmentioning

confidence: 99%

Persistence of oral antidiabetic treatment for type 2 diabetes characterized by drug class, patient characteristics and severity of renal impairment: A Japanese database analysis

Kadowaki

Sarai

Hirakawa

et al. 2018

Diabetes Obesity Metabolism

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show abstract

“…Linagliptin is primarily nonrenally excreted: 80% of the drug is eliminated via the bile and gut and only 5% is eliminated via the kidney [31] . The drug is not practically metabolized and is excreted unchanged.…”

Section: Linagliptinmentioning

confidence: 99%

Diabetes treatment in patients with renal disease: Is the landscape clear enough?

Ioannidis¹

2014

WJD

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Diabetes is the most important risk factors for chronic kidney disease (CKD). The risk of CKD attributable to diabetes continues to rise worldwide. Diabetic patients with CKD need complicated treatment for their metabolic disorders as well as for related comorbidities. They have to treat, often intensively, hypertension, dyslipidaemia, bone disease, anaemia, and frequently established cardiovascular disease. The treatment of hypoglycaemia in diabetic persons with CKD must tie their individual goals of glycaemia (usually less tight glycaemic control) and knowledge on the pharmacokinetics and pharmacodynamics of drugs available to a person with kidney disease. The problem is complicated from the fact that in many efficacy studies patients with CKD are excluded so data of safety and efficacy for these patients are missing. This results in fear of use by lack of evidence. Metformin is globally accepted as the first choice in practically all therapeutic algorithms for diabetic subjects. The advantages of metformin are low risk of hypoglycaemia, modest weight loss, effectiveness and low cost. Data of UKPDS indicate that treatment based on metformin results in less total as well cardiovascular mortality. Metformin remains the drug of choice for patients with diabetes and CKD provided that their estimate Glomerular Filtration Rate (eGFR) remains above 30 mL/min per square meter. For diabetic patients with eGFR between 30-60 mL/min per square meter more frequent monitoring of renal function and dose reduction of metformin is needed. The use of sulfonylureas, glinides and insulin carry a higher risk of hypoglycemia in these patients and must be very careful. Lower doses and slower titration of the dose is needed. Is better to avoid sulfonylureas with active hepatic metabolites, which are renally excreted. Very useful drugs for this group of patients emerge dipeptidyl peptidase 4 inhibitors. These drugs do not cause hypoglycemia and most of them (linagliptin is an exception) require dose reduction in various stages of renal disease.

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“…The most clinically specificity of linagliptin compared with other available DPP-4 inhibitors concerns its minimal renal excretion 29,44 . We have reviewed the PK properties of linagliptin, as compared with those of other DPP-4 inhibitors, emphasizing its negligible renal excretion and its low potential of DDIs 29,63 .…”

Section: Linagliptinmentioning

confidence: 99%

“…The most clinically relevant specificity, relative to other already available DPP-4 inhibitors, is that linagliptin has a minimal renal excretion and instead a predominant biliary excretion 29,44 . Thus, it may be used in patients with chronic kidney disease (CKD) without dose adjustment 44 . This contrasts with other DPP-4 inhibitors, for which a dose reduction is recommended according to the decrease of the estimated glomerular filtration rate (eGFR) 45 .…”

Section: Introductionmentioning

confidence: 99%

Linagliptin plus metformin: a pharmacokinetic and pharmacodynamic evaluation

Scheen

2013

Expert Opinion on Drug Metabolism & Toxicology

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SUMMARYIntroduction : The first-choice drug therapy in the management of type 2 diabetes is metformin. However, most patients require a combined therapy to reach and/or maintain targets of glucose control. Dipeptidylpeptidase-4 (DPP-4) inhibitors, commonly referred to as gliptins, offer new options for combined therapy with metformin. Linagliptin is the most recent launched gliptin, with a unique pharmacokinetic profile characterized by negligible renal excretion, and is now also available as a fixed-dose combination (FDC) with metformin.Area covered: An extensive literature search was performed to analyze the potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between linagliptin and metformin. Linaglipin and metformin may be administered together, either separately or as FDC supported by bioequivalence studies. Linagliptin and metformin are not prone to PK drug-drug interactions. Their co-administration improves blood glucose control more potently than either compound separately, without hypoglycemia and without increasing metforminrelated gastrointestinal side effects.Expert Opinion : The combination linaglitpin plus metformin, if not contraindicated (renal failure), may be used as first-line or second-line therapy in the management of type 2 diabetes.

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Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin*

Abstract: Renal impairment has only a minor effect on linagliptin pharmacokinetics. Consequently, there will be no need for adjusting the linagliptin dose in renally impaired patients with T2DM.

Cited by 168 publications

References 15 publications

Persistence of oral antidiabetic treatment for type 2 diabetes characterized by drug class, patient characteristics and severity of renal impairment: A Japanese database analysis

Persistence of oral antidiabetic treatment for type 2 diabetes characterized by drug class, patient characteristics and severity of renal impairment: A Japanese database analysis

Diabetes treatment in patients with renal disease: Is the landscape clear enough?

Linagliptin plus metformin: a pharmacokinetic and pharmacodynamic evaluation

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