Understanding how pharmacokinetic and pharmacodynamic differences of basal analog insulins influence clinical practice

Current Medical Research and Opinion

Volumn 33, Issue 10, 2017, Pages 1821-1831

  Goldman, Jennifer ^a   Kapitza, Christoph ^b   Pettus, Jeremy ^c   Heise, Tim ^b  

^a MASSACHUSETTS COLLEGE OF PHARMACY AND HEALTH SCIENCES   (United States)

^b Profil   (Germany)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

diabetes mellitus; Insulins; pharmacodynamics; pharmacokinetics

Indexed keywords

BASAL INSULIN ANALOG; INSULIN DEGLUDEC; INSULIN DERIVATIVE; INSULIN DETEMIR; INSULIN GLARGINE; UNCLASSIFIED DRUG; ANTIDIABETIC AGENT; LONG ACTING INSULIN;

CLINICAL PRACTICE; EUGLYCEMIC CLAMP TECHNIQUE; GLUCOSE CLAMP TECHNIQUE; HUMAN; PHARMACODYNAMICS; REVIEW; STEADY STATE; DRUG EFFECTS; GLUCOSE BLOOD LEVEL; HYPOGLYCEMIA; INSULIN DEPENDENT DIABETES MELLITUS; NON INSULIN DEPENDENT DIABETES MELLITUS;

BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; HUMANS; HYPOGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN, LONG-ACTING;

EID: 85029373158     PISSN: 03007995     EISSN: 14734877     Source Type: Journal    
DOI: 10.1080/03007995.2017.1335192     Document Type: Review

References (95)

1. Heise T, Meneghini LF., Insulin stacking versus therapeutic accumulation:understanding the differences. Endocr Pract 2014;20:75-83
2. Home PD., Plasma insulin profiles after subcutaneous injection:how close can we get to physiology in people with diabetes? Diabetes Obes Metab 2015;17:1011-20
3. Evans M, Schumm-Draeger PM, Vora J, et al. A review of modern insulin analogue pharmacokinetic and pharmacodynamic profiles in type 2 diabetes:improvements and limitations. Diabetes Obes Metab 2011;13:677-84
4. Abrahamson MJ., Basal insulins:pharmacological properties and patient perspectives. Prim Care Diabetes 2010;4(Suppl 1):S19-S23
5. Scholtz HE, Pretorius SG, Wessels DH, et al. Pharmacokinetic and glucodynamic variability:assessment of insulin glargine, NPH insulin and insulin ultralente in healthy volunteers using a euglycaemic clamp technique. Diabetologia 2005;48:1988-95
6. Tibaldi JM., Evolution of insulin development:focus on key parameters. Adv Ther 2012;29:590-619
7. Tibaldi JM., Evolution of insulin:from human to analog. Am J Med 2014;127(10 Suppl):S25-S38
8. King A, Clark D, Wolfe G., Contribution of the dawn phenomenon to the fasting and postbreakfast hyperglycemia in type 1 diabetes treated with once-nightly insulin glargine. Endocr Pract 2012;18:558-62
9. Yagasaki H, Kobayashi K, Saitou T, et al. Nocturnal blood glucose and IGFBP-1 changes in type 1 diabetes:differences in the dawn phenomenon between insulin regimens. Exp Clin Endocrinol Diabetes 2010;118:195-9
10. Arnolds S, Kuglin B, Kapitza C, et al. How pharmacokinetic and pharmacodynamic principles pave the way for optimal basal insulin therapy in type 2 diabetes. Int J Clin Pract 2010;64:1415-24
11. Porcellati F, Bolli GB, Fanelli CG., Pharmacokinetics and pharmacodynamics of basal insulins. Diabetes Technol Ther 2011;13(Suppl 1):S15-S24
12. Swinnen SG, Holleman F, DeVries JH., The interpretation of glucose clamp studies of long-acting insulin analogues:from physiology to marketing and back. Diabetologia 2008;51:1790-5
13. Heise T, Pieber TR., Towards peakless, reproducible and long-acting insulins. An assessment of the basal analogues based on isoglycaemic clamp studies. Diabetes Obes Metab 2007;9:648-59
14. Heise T, Korsatko S, Nosek L, et al. Steady state is reached within 2–3 days of once-daily administration of degludec, a basal insulin with an ultralong duration of action. J Diabetes 2016;8:132-8
15. Heise T, Bott S, Rave K, et al. No evidence for accumulation of insulin glargine (LANTUS):a multiple injection study in patients with type 1 diabetes. Diabet Med 2002;19:490-5
16. Bott S, Tusek C, Jacobsen LV, et al. Insulin detemir under steady-state conditions:no accumulation and constant metabolic effect over time with twice daily administration in subjects with type 1 diabetes. Diabet Med 2006;23:522-8
17. Aye MM, Atkin SL., Patient safety and minimizing risk with insulin administration–role of insulin degludec. Drug Healthc Patient Saf 2014;6:55-67
18. Danne T, Becker RH, Ping L, et al. Insulin glargine metabolite 21(A)-Gly-human insulin (M1) is the principal component circulating in the plasma of young children with type 1 diabetes:results from the PRESCHOOL study. Pediatr Diabetes 2015;16:299-304
19. Arutchelvam V, Heise T, Dellweg S, et al. Plasma glucose and hypoglycaemia following exercise in people with type 1 diabetes:a comparison of three basal insulins. Diabet Med 2009;26:1027-32
20. Heise T, Bain SC, Bracken RM, et al. Similar risk of exercise-related hypoglycaemia for insulin degludec to that for insulin glargine in patients with type 1 diabetes:a randomized cross-over trial. Diabetes Obes Metab 2016;18:196-9
21. Riddell MC, Gallen IW, Smart CE, et al. Exercise management in type 1 diabetes:a consensus statement. Lancet Diabetes Endocrinol 2017;5:377-90
22. Levemir Prescribing Information. Novo Nordisk website. Available at:http://www.novo-pi.com/levemir.pdf [Last accessed 8 May 2017]
23. Heinemann L, Sinha K, Weyer C, et al. Time–action profile of the soluble, fatty acid acylated, long-acting insulin analogue NN304. Diabet Med 1999;16:332-8
24. Havelund S, Plum A, Ribel U, et al. The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharm Res 2004;21:1498-504
25. Brunner GA, Sendhofer G, Wutte A, et al. Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans. Exp Clin Endocrinol Diabetes 2000;108:100-5
26. Klein O, Lynge J, Endahl L, et al. Albumin-bound basal insulin analogues (insulin detemir and NN344):comparable time–action profiles but less variability than insulin glargine in type 2 diabetes. Diabetes Obes Metab 2007;9:290-9
27. Rosenstock J, Davies M, Home PD, et al. A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia 2008;51:408-16
28. Koehler G, Treiber G, Wutte A, et al. Pharmacodynamics of the long-acting insulin analogues detemir and glargine following single-doses and under steady-state conditions in patients with type 1 diabetes. Diabetes Obes Metab 2014;16:57-62
29. Plank J, Bodenlenz M, Sinner F, et al. A double-blind, randomized, dose–response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir. Diabetes Care 2005;28:1107-12
30. Home P, Bartley P, Russell-Jones D, et al. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes:a randomized clinical trial. Diabetes Care 2004;27:1081-7
31. Hermansen K, Davies M, Derezinski T, et al. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care 2006;29:1269-74
32. Philis-Tsimikas A, Charpentier G, Clauson P, et al. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther 2006;28:1569-81
33. Raslová K, Tamer SC, Clauson P, et al. Insulin detemir results in less weight gain than NPH insulin when used in basal–bolus therapy for type 2 diabetes mellitus, and this advantage increases with baseline body mass index. Clin Drug Investig 2007;27:279-85
34. Kuerzel GU, Shukla U, Scholtz HE, et al. Biotransformation of insulin glargine after subcutaneous injection in healthy subjects. Curr Med Res Opin 2003;19:34-40
35. Steinstraesser A, Schmidt R, Bergmann K, et al. Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/m. Diabetes Obes Metab 2014;16:873-6
36. Lantus Prescribing Information. Sanofi website. Available at:http://products.sanofi.us/lantus/lantus.pdf [Last accessed 8 May 2017]
37. Heise T, Hövelmann U, Nosek L, et al. Insulin degludec has a two-fold longer half-life and a more consistent pharmacokinetic profile compared with insulin glargine. Endocrine Abstracts 2012;28:P188
38. Lepore M, Pampanelli S, Fanelli C, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes 2000;49:2142-8
39. Hirsch IB., Insulin analogues. N Engl J Med 2005;352:174-83
40. Becker RH, Frick AD, Teichert L, et al. Fluctuation and reproducibility of exposure and effect of insulin glargine in healthy subjects. Diabetes Obes Metab 2008;10:1105-13
41. Rosenstock J, Park G, Zimmerman J; US, Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group. Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. Diabetes Care 2000;23:1137-42
42. Raskin P, Klaff L, Bergenstal R, et al. A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes. Diabetes Care 2000;23:1666-71
43. Home PD, Rosskamp R, Forjanic-Klapproth J, et al. A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes. Diabetes Metab Res Rev 2005;21:545-53
44. Rosenstock J, Dailey G, Massi-Benedetti M, et al. Reduced hypoglycemia risk with insulin glargine:a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes. Diabetes Care 2005;28:950-5
45. Siegmund T, Weber S, Blankenfeld H, et al. Comparison of insulin glargine versus NPH insulin in people with type 2 diabetes mellitus under outpatient-clinic conditions for 18 months using a basal–bolus regimen with a rapid-acting insulin analogue as mealtime insulin. Exp Clin Endocrinol Diabetes 2007;115:349-53
46. Meneghini L, Kesavadev J, Demissie M, et al. Once-daily initiation of basal insulin as add-on to metformin:a 26-week, randomized, treat-to-target trial comparing insulin detemir with insulin glargine in patients with type 2 diabetes. Diabetes Obes Metab 2013;15:729-36
47. Albright ES, Desmond R, Bell DSH., Efficacy of conversion from bedtime NPH insulin injection to once- or twice-daily injections of insulin glargine in type 1 diabetic patients using basal/bolus therapy. Diabetes Care 2004;27:632-3
48. Pieber TR, Treichel HC, Hompesch B, et al. Comparison of insulin detemir and insulin glargine in subjects with type 1 diabetes using intensive insulin therapy. Diabet Med 2007;24:635-42
49. Heller S, Koenen C, Bode B., Comparison of insulin detemir and insulin glargine in a basal–bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes:a 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial. Clin Ther 2009;31:2086-97
50. ORIGIN Trial Investigators, Gerstein HC, Bosch J, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012;367:319-28
51. Fagot JP, Blotière PO, Ricordeau P, et al. Does insulin glargine increase the risk of cancer compared with other basal insulins? A French nationwide cohort study based on national administrative databases. Diabetes Care 2013;36:294-301
52. Tang X, Yang L, He Z, et al. Insulin glargine and cancer risk in patients with diabetes:a meta-analysis. PLoS One 2012;7:e51814
53. −1. Diabetes Care 2015;38:637-43
54. Toujeo Prescribing Information. Sanofi website. Available at:http://products.sanofi.us/toujeo/toujeo.pdf [Last accessed 8 May 2017]
55. Becker RH, Nowotny I, Teichert L, et al. Low within- and between-day variability in exposure to new insulin glargine 300 U/ml. Diabetes Obes Metab 2015;17:261-7
56. Shiramoto M, Eto T, Irie S, et al. Single-dose new insulin glargine 300 U/ml provides prolonged, stable glycaemic control in Japanese and European people with type 1 diabetes. Diabetes Obes Metab 2015;17:254-60
57. Ritzel R, Roussel R, Bolli GB, et al. Patient-level meta-analysis of the EDITION 1, 2 and 3 studies:glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes. Diabetes Obes Metab 2015;17:859-67
58. Matsuhisa M, Koyama M, Cheng X, et al. New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese adults with type 1 diabetes using basal and mealtime insulin:glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 1). Diabetes Obes Metab 2016;18:375-83
59. Home PD, Bergenstal RM, Bolli GB, et al. New insulin glargine 300 units/ml versus glargine 100 units/mL in people with type 1 diabetes:a randomized, phase 3a, open-label clinical trial (EDITION 4). Diabetes Care 2015;38:2217-25
60. ClinicalTrials.gov. A Study Comparing the Efficacy and Safety of the Morning Injection of Toujeo Versus Lantus in Patients With Type 1 Diabetes Mellitus. Available at:https://clinicaltrials.gov/ct2/show/NCT02688933 [Last accessed 8 May 2017]
61. Riddle MC, Bolli GB, Ziemen M, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin:glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1). Diabetes Care 2014;37:2755-62
62. Riddle MC, Yki-Järvinen H, Bolli GB, et al. One year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/mL compared with 100 U/mL in people with type 2 diabetes using basal + meal-time insulin (EDITION 1 12-month randomized trial including 6-month extension). Diabetes Obes Metab 2015;17:835-42
63. Yki-Järvinen H, Bergenstal R, Ziemen M, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin:glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2). Diabetes Care 2014;37:3235-43
64. Yki-Järvinen H, Bergenstal RM, Bolli GB, et al. Less nocturnal hypoglycaemia and weight gain with new insulin glargine 300 U/ml vs 100 U/ml:1-year results in people with type 2 diabetes using basal insulin and OADs (EDITION 2) [abstract 946]. Diabetologia 2014;57(Suppl 1):S387
65. Bolli GB, Riddle MC, Bergenstal RM, et al. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs:a randomized controlled trial (EDITION 3). Diabetes Obes Metab 2015;17:386-94
66. Matsuhisa M, Koyama M, Cheng X, et al.; EDITION JP 1 study group. Sustained glycaemic control and less nocturnal hypoglycaemia with insulin glargine 300U/mL compared with glargine 100U/mL in Japanese adults with type 1 diabetes (EDITION JP 1 randomised 12-month trial including 6-month extension). Diabetes Res Clin Pract 2016;122:133-40
67. Terauchi Y, Koyama M, Cheng X, et al.; on behalf of the EDITION JP 2 Study Group. Glycaemic control and hypoglycaemia in Japanese people with type 2 diabetes mellitus receiving new insulin glargine 300 U/mL in combination with OADs (EDITION JP 2) [abstract 976]. Diabetologia 2014;57(Suppl 1):S401
68. Terauchi Y, Koyama M, Cheng X, et al.; on behalf of the EDITION JP 2 Study Group. New insulin glargine 300 U/mL provides sustained glycemic control and reduced hypoglycemia over 12 months compared with glargine 100 U/mL in Japanese people with T2DM managed with basal insulin plus OAD(s) (EDITION JP 2) [abstract 98-OR]. Diabetes 2015;64(Suppl 1):A26
69. Goldman J, White JR, Jr.New insulin glargine 300 U/mL for the treatment of type 1 and type 2 diabetes mellitus. Ann Pharmacother 2015;49:1153-61
70. Toujeo Summary of Product Characteristics. Website. Available at:http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000309/WC500047935.pdf [Last accessed 8 May 2017]
71. 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 [abstract]. Diabetologia 2011;54(Suppl 1):S426
72. 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
73. Korsatko S, Deller S, Koehler G, et al. A comparison of the steady-state pharmacokinetic and pharmacodynamic profiles of 100 and 200 U/mL formulations of ultra-long-acting insulin degludec. Clin Drug Investig 2013;33:515-21
74. Bode BW, Chaykin LB, Sussman AM, et al. Efficacy and safety of insulin degludec 200 U/mL and insulin degludec 100 U/mL in patients with type 2 diabetes (Begin:Compare). Endocr Pract 2014;20:785-91
75. Novo Nordisk. Tresiba Prescribing Information. Available at:http://www.novo-pi.com/tresiba.pdf [Last accessed 8 May 2017]
76. 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
77. Haahr H, Heise T., A review of the pharmacological properties of insulin degludec and their clinical relevance. Clin Pharmacokinet 2014;53:787-800
78. Heise T, Hermanski L, Nosek L, et al. H. 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
79. Bailey T, Dahmen R, Pettus J, et al. Insulin glargine 300 U/mL (Gla-300) provides more stable and more evenly distributed steady-state pharmacodynamic/pharmacokinetic profiles compared with insulin degludec in type 1 diabetes (T1DM). Endocr Pract 2017;23;1-48A
80. Heise T, Nørskov M, Nosek L, et al. Insulin degludec:lower day-to-day and within-day variability in pharmacodynamic response compared to insulin glargine U300 in type 1 diabetes. Diabetes Obes Metab. 2017;19:1032-1039
81. ClinicalTrials.gov. Toujeo Tresiba in Insulin-Naive Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Antihyperglycemic Drug(s) ± GLP-1 Receptor Agonist. Available at:https://clinicaltrials.gov/ct2/show/NCT02738151 [Last accessed 8 May 2017]
82. Heller S, Buse J, Fisher M, et al. Insulin degludec, an ultra-longacting 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
83. Mathieu C, Hollander P, Miranda-Palma B, et al. Efficacy and safety of insulin degludec in a flexible dosing regimen vs insulin glargine in patients with type 1 diabetes (BEGIN:Flex T1):a 26-week randomized, treat-to-target trial with a 26-week extension. J Clin Endocrinol Metab 2013;98:1154-62
84. Zinman B, Philis-Tsimikas A, Cariou B, et al. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes:a 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care 2012;35:2464-71
85. 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
86. Gough SC, Bhargava A, Jain R, et al. Low-volume insulin degludec 200 units/ml once daily improves glycemic control similarly to insulin glargine with a low risk of hypoglycemia in insulin-naive patients with type 2 diabetes:a 26-week, randomized, controlled, multinational, treat-to-target trial:the BEGIN LOW VOLUME trial. Diabetes Care 2013;36:2536-42
87. Rodbard HW, Gough S, Lane W, et al. Reduced risk of hypoglycemia with insulin degludec versus insulin glargine in patients with type 2 diabetes requiring high doses of basal insulin:a meta-analysis of 5 randomized begin trials. Endocr Pract 2014;20:285-92
88. United Food and Drug Administration website. Biosimilars. Available at:www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm241718.htm [Last accessed 8 May 2017]
89. Eli Lilly website. Press release, 2014. European Commission grants Lilly and Boehringer Ingelheim’s insulin glargine product marketing authorisation in Europe. Available at:https://investor.lilly.com/releasedetail.cfm?ReleaseID=870088 [Last accessed 8 May 2017]
90. DeVries JH, Gough SC, Kiljanski J, et al. Biosimilar insulins:a European perspective. Diabetes Obes Metab 2015;17:445-51
91. Linnebjerg H, Lam EC, Seger ME, et al. Comparison of the pharmacokinetics and pharmacodynamics of LY2963016 insulin glargine and EU- and US-approved versions of Lantus insulin glargine in healthy subjects:three randomized euglycemic clamp studies. Diabetes Care 2015;38:2226-33
92. Rosenstock J, Hollander P, Bhargava A, et al. Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine:a randomized, double-blind controlled trial (the ELEMENT 2 study). Diabetes Obes Metab 2015;17:734-41
93. Ashwell SG, Gebbie J, Home PD., Twice-daily compared with once-daily insulin glargine in people with type 1 diabetes using meal-time insulin aspart. Diabet Med 2006;23:879-86
94. Meneghini L, Atkin SL, Gough SC, et al. The efficacy and safety of insulin degludec given in variable once-daily dosing intervals compared with insulin glargine and insulin degludec dosed at the same time daily:a 26-week, randomized, open-label, parallel-group, treat-to-target trial in individuals with type 2 diabetes. Diabetes Care 2013;36:858-64
95. Jeandidier N, Riddle MC, Bolli GB, et al. New insulin glargine 300 U/ml:efficacy and safety of flexible vs fixed dosing intervals in people with type 2 diabetes mellitus [abstract]. Diabetologia 2014;57(Suppl 1):S393(Abstract 961)