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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 2/2014

Open Access 01-02-2014 | Original Research Article

Insulin Degludec: Pharmacokinetics in Patients with Renal Impairment

Authors: István Kiss, Gerhard Arold, Carsten Roepstorff, Susanne Gammelgaard Bøttcher, Søren Klim, Hanne Haahr

Published in: Clinical Pharmacokinetics | Issue 2/2014

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Abstract

Background

Insulin degludec is a new-generation basal insulin with an ultra-long duration of action. We evaluated the pharmacokinetic properties of insulin degludec in subjects with normal renal function; mild, moderate or severe renal impairment; or end-stage renal disease (ESRD) undergoing hemodialysis.

Methods

Thirty subjects (n = 6 per group) received a single subcutaneous dose of 0.4 U/kg insulin degludec. Blood samples up to 120 h post-dose and fractionated urine samples were collected.

Results

The ultra-long pharmacokinetic properties of insulin degludec were preserved in subjects with renal impairment, with no statistically significant differences in absorption or clearance, compared with subjects with normal renal function. In subjects with ESRD, pharmacokinetic parameters were similar whether the insulin degludec pharmacokinetic assessment period included hemodialysis or not, and total exposure was comparable to subjects with normal renal function. Simulated mean steady-state pharmacokinetic profiles were comparable between groups.

Conclusion

This study indicated dose adjustments due to impaired renal function should not be required for insulin degludec.
Literature
1.
Cavanaugh KL. Diabetes management issues for patients with chronic kidney disease. Clinical Diabetes. 2007;25:90–7.CrossRef
2.
de Boer IH, Rue TC, Hall YN, et al. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA. 2001;305:2532–9.CrossRef
3.
Middleton RJ, Foley RN, Hegarty J, et al. The unrecognized prevalence of chronic kidney disease in diabetes. Nephrol Dial Transplant. 2006;21:88–92.PubMedCrossRef
4.
Assogba GF, Couchoud C, Roudier C, et al. Prevalence, screening and treatment of chronic kidney disease in people with type 2 diabetes in France: the ENTRED surveys (2001 and 2007). Diabetes Metab. 2012;38:558–66.PubMedCrossRef
5.
New JP, Middleton RJ, Klebe B, et al. Assessing the prevalence, monitoring and management of chronic kidney disease in patients with diabetes compared with those without diabetes in general practice. Diabet Med. 2007;24:364–9.PubMedCrossRef
6.
Harvey JN. Trends in the prevalence of diabetic nephropathy in type 1 and type 2 diabetes. Curr Opin Nephrol Hypertens. 2003;12:317–22.PubMedCrossRef
7.
8.
Biesenbach G, Raml A, Schmekal B, Eichbauer-Sturm G. Decreased insulin requirement in relation to GFR in nephropathic type 1 and insulin-treated type 2 diabetic patients. Diabet Med. 2003;20:642–5.PubMedCrossRef
9.
Moen MF, Zhan M, Hsu VD, et al. Frequency of hypoglycemia and its significance in chronic kidney disease. Clin J Am Soc Nephrol. 2009;2009(4):1121–7.CrossRef
10.
11.
Muhlhauser I, Toth G, Sawicki PT, Berger M. Severe hypoglycemia in type I diabetic patients with impaired kidney function. Diabetes Care. 1991;14:344–6.PubMedCrossRef
12.
13.
Farrokhi F, Klindukhova O, Chandra P, et al. Risk factors for inpatient hypoglycemia during subcutaneous insulin therapy in non-critically ill patients with type 2 diabetes. J Diabetes Sci Technol. 2012;6:1022–9.PubMedCentralPubMedCrossRef
14.
Scheen AJ. Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease. Expert Opin Drug Metab Toxicol. 2013;9:529–50.PubMedCrossRef
15.
Snyder RW, Berns JS. Use of insulin and oral hypoglycemic medications in patients with diabetes mellitus and advanced kidney disease. Semin Dial. 2004;17:365–70.PubMedCrossRef
16.
Rave K, Heise T, Pfützner A, et al. Impact of diabetic nephropathy on pharmacodynamic and pharmacokinetic properties of insulin in type 1 diabetic patients. Diabetes Care. 2001;24:886–90.PubMedCrossRef
17.
Holmes G, Galitz L, Hu P, Lyness W. Pharmacokinetics of insulin aspart in obesity, renal impairment, or hepatic impairment. Br J Clin Pharmacol. 2005;60:469–76.PubMedCrossRef
18.
Lynes W, Tyler JF, Lawrence A. Renal impairment does not affect insulin aspart pharmacokinetics in type 1 diabetes. Diabetes. 2001;50(suppl 2):A441–2.
19.
20.
Jacobsen LV, Popescu G, Plum A. Pharmacokinetics of insulin detemir in subjects with renal or hepatic impairment. Diabetologia. 2002;45(suppl 1):A259.
21.
Kurtzhals P, Heise T, Strauss HM, et al. Multi-hexamer formation is the underlying basis for the ultra-long glucose-lowering effect of insulin degludec. Diabetologia. 2011;54(Suppl 1):S426.
22.
Jonassen I, Havelund S, Hoeg-Jensen T, et al. Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin. Pharm Res. 2012;29:2104–14.PubMedCentralPubMedCrossRef
23.
Heise T, Nosek L, Bøttcher SG, et al. Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes. Diabetes Obes Metab. 2012;14:944–50.PubMedCrossRef
24.
Heise T, Hermanski L, Nosek L, et al. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab. 2012;14:859–64.PubMedCrossRef
25.
Birkeland KI, Home PD, Wendisch U, et al. Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine. Diabetes Care. 2011;34:661–5.PubMedCrossRef
26.
Heller S, Buse J, Fisher M, et al. Insulin degludec, an ultra-long-acting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet. 2012;379:1489–97.PubMedCrossRef
27.
Garber AJ, King AB, Del Prato S, et al. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet. 2012;379:1498–507.PubMedCrossRef
28.
Ratner RE, Gough SC, Mathieu C, et al. Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab. 2013;15:175–84.PubMedCentralPubMedCrossRef
29.
30.
31.
American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005;28:1245–9.CrossRef
32.
33.
Baldwin D, Zander J, Munoz C, et al. A randomized trial of two weight-based doses of insulin glargine and glulisine in hospitalized subjects with type 2 diabetes and renal insufficiency. Diabetes Care. 2012;35:1970–4.PubMedCrossRef
34.
Pscherer S, Schreyer-Zell G, Gottsmann M. Experience with insulin glargine in patients with end-stage renal disease. Diabetes. 2002;216-OR:A53.
35.
36.
37.
38.
39.
Metadata
Title
Insulin Degludec: Pharmacokinetics in Patients with Renal Impairment
Authors
István Kiss
Gerhard Arold
Carsten Roepstorff
Susanne Gammelgaard Bøttcher
Søren Klim
Hanne Haahr
Publication date
01-02-2014
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 2/2014
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-013-0113-2

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