Pharmacokinetics of repaglinide in subjects with renal impairment

Marbury, Thomas; Ruckle, Jon; Hatorp, Vibeke; Andersen, Michael; Nielsen, Kristina Tomra; Huang, Won Chin; Strange, Poul

doi:10.1067/mcp.2000.103973

Cited by 99 publications

(67 citation statements)

References 9 publications

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“…Repaglinide was safe and well tolerated in subjects with varying degrees of RI. Although adjustment of starting doses of repaglinide is not necessary for RI or renal failure, severe impairment may require more care when upward adjustments of dosage are made 89 .…”

Section: Repaglinidementioning

confidence: 99%

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Scheen¹

2013

Expert Opinion on Drug Metabolism & Toxicology

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SUMMARYIntroduction : People with chronic kidney disease (CKD) of stages 3-5 (creatinine clearance < 60 ml/min) represent 25-30% of patients with type 2 diabetes (T2DM), but the problem is underrecognized or neglected in clinical practice. However, most oral antidiabetic agents have limitations in case of renal impairment, either because they require a dose adjustment or because they are contraindicated for safety reasons. Expert Opinion : Because of potential important PK interferences and for safety reasons, the pharmacological management of T2DM should be adjusted according to kidney function. In general, the daily dose should be reduced according to glomerular filtration rate (GFR) or even the drug is contraindicated in presence of more severe CKD. This is the case for metformin (risk of lactic acidosis) and for many sulfonylureas (risk of hypoglycemia). At present, however, the exact GFR cutoff for metformin use is controversial. New antidiabetic agents are better tolerated in case of CKD, although clinical experience remains quite limited for most of them. The dose of DPP-4 inhibitors should be reduced (except for linaglitpin) whereas both the efficacy and safety of SGLT2 inhibitors are questionable in presence of CKD.

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Section: Repaglinidementioning

confidence: 99%

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Scheen¹

2013

Expert Opinion on Drug Metabolism & Toxicology

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“…The major metabolites of repaglinide are M1, M2 and M4. These metabolites are excreted via the bile into the feces and have no hypoglycemic activity [20] . Repaglinide can be used even in CKD stages 4 and 5 without dose reduction.…”

Section: Glinidesmentioning

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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“…However, two previous short-term clinical studies on the pharmacokinetics of repaglinide in subjects with renal impairment showed some slight differences compared with patients with normal renal function (10,11). One study showed that the area under the curve (AUC) and maximum serum concentration (C max ) for repaglinide were significantly higher in subjects with renal impairment than in healthy subjects, but were independent of the degree of renal impairment (10).…”

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confidence: 99%

Safety and Efficacy of Repaglinide in Type 2 Diabetic Patients With and Without Impaired Renal Function

Hasslacher¹

2003

Diabetes Care

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OBJECTIVE -To evaluate the influence of renal impairment on the safety and efficacy of repaglinide in type 2 diabetic patients. RESEARCH DESIGN AND METHODS -This multinational, open-label study comprised a 6-week run-in period, continuing prestudy antidiabetic medication, followed by a titration period (1-4 weeks) and a 3-month maintenance period. Patients with normal renal function (n ϭ 151) and various degrees of renal impairment (n ϭ 130) were treated with repaglinide (maximal dose of 4 mg, three times daily). Safety and efficacy assessments were performed at baseline (end of run-in) and at the end of study treatment.RESULTS -The type and severity of adverse events during repaglinide treatment were similar to the run-in period. The number of patients with adverse events was not significantly related to renal function during run-in or repaglinide treatment. Percentage of patients with hypoglycemic episodes increased significantly (P ϭ 0.007) with increasing severity of renal impairment during run-in but not during repaglinide treatment (P ϭ 0.074). Metabolic control (HbA 1c and fasting blood glucose) with repaglinide was unchanged from that on previous antidiabetic medication. Final repaglinide dose tended to be lower for patients with severe and extreme renal impairment than for patients with less severe renal impairment or normal renal function (P ϭ 0.032).CONCLUSIONS -Repaglinide has a good safety and efficacy profile in type 2 diabetic patients complicated by renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal impairment.

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Pharmacokinetics of repaglinide in subjects with renal impairment

Abstract: Repaglinide was safe and well tolerated in subjects with varying degrees of renal impairment. Although adjustment of starting doses of repaglinide is not necessary for renal impairment or renal failure, severe impairment may require more care when upward adjustments of dosage are made.

Cited by 99 publications

References 9 publications

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

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

Safety and Efficacy of Repaglinide in Type 2 Diabetic Patients With and Without Impaired Renal Function

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