Objective: To review 2 new basal insulin analogs that have been approved in the United States for use in type 1 and type 2 diabetes—insulin glargine 300 units/mL and insulin degludec 100 units/mL and 200 units/mL. Data Sources: PubMed was searched using the terms “insulin glargine 300 units/mL,” “Gla-300,” “insulin degludec,” “IDeg,” “insulin degludec 200 units/mL,” and “insulin degludec 100 units/mL” for articles published between 1995 and May 2016. Study Selection and Data Extraction: Clinical trials, meta-analyses and subanalyses were identified; review articles were excluded. Relevant citations from identified articles were also reviewed. Data Synthesis: The new basal insulins, insulin glargine 300 units/mL and insulin degludec 100 units/mL and 200 units/mL, have improved pharmacokinetic and pharmacodynamic profiles compared to insulin glargine 100 units/mL. All demonstrate longer durations of action, beyond 24 hours, and less variability. These improved profiles translate into comparable A1C reductions and comparable, or improved, levels of hypoglycemia compared to insulin glargine 100 units/mL. Conclusions: These benefits may lead to improved glycemic control in a range of patients with type 1 and type 2 diabetes with true once-daily dosing.
TibaldiJM. Evolution of insulin development: focus on key parameters. Adv Ther. 2012;29:590-619.
2.
ArnoldsSKuglinBKapitzaCHeiseT. How pharmacokinetic and pharmacodynamic principles pave the way for optimal basal insulin therapy in type 2 diabetes. Int J Clin Pract. 2010;64:1415-1424.
3.
TibaldiJM. Evolution of insulin: from human to analog. Am J Med. 2014;127(suppl 10):S25-S38.
4.
LeporeMPampanelliSFanelliC. 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;49:2142-2148.
5.
PorcellatiFRossettiPBusciantellaNR. Comparison of pharmacokinetics and dynamics of the long-acting insulin analogs glargine and detemir at steady state in type 1 diabetes: a double-blind, randomized, crossover study. Diabetes Care. 2007;30:2447-2452.
6.
HeiseTPieberTR. Towards peakless, reproducible and long-acting insulins. An assessment of the basal analogues based on isoglycemic clamp studies. Diabetes Obes Metab. 2007;9:648-659.
7.
MonamiMMarchionniNMannucciE. Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract. 2008;81:184-189.
8.
MonamiMMarchionniNMannucciE. Long-acting insulin analogues vs. NPH human insulin in type 1 diabetes. A meta-analysis. Diabetes Obes Metab. 2009;11:372-378.
9.
BeckerRHDahmenRBergmannKLehmannAJaxTHeiseT. New insulin glargine 300 units mL−1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 units mL−1. Diabetes Care. 2014;38:637-643.
10.
ShiramotoMEtoTIrieS. 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;17:254-260.
11.
BeckerRHNowotnyITeichertLBergmannKKapitzaC. Low within- and between-day variability in exposure to new insulin glargine 300 U mL−1. Diabetes Obes Metab. 2015;17:261-267.
12.
KorsatkoSDellerSKoehlerG. 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;33:515-521.
13.
HeiseTHövelmannUNosekLHermanskiLBøttcherSGHaahrH. Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine. Expert Opin Drug Metab Toxicol. 2015;11:1193-1201.
14.
SteinstraesserASchmidtRBergmannKDahmenRBeckerRHA. Investigational new insulin glargine 300 U/mL has the same metabolism as insulin glargine 100 U/mL. Diabetes Obes Metab. 2014;16:873-876.
15.
ORIGIN Trial Investigators; GersteinHCBoschJDagenaisGR. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367:319-328.
16.
RiddleMCBolliGBZiemenMMuehlen-BartmerIBizetFHomePD. 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;37:2755-2762.
17.
Yki-JärvinenHBergenstalRZiemenM. 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;37:3235-3243.
18.
BolliGBRiddleMCBergenstalRM. 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;17:386-394.
19.
HomePDBergenstalRMBolliGB. 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;38:2217-2225.
20.
RiddleMCBolliGBHomePD. Efficacy and safety of flexible versus fixed dosing intervals of insulin glargine 300 U/mL in people with type 2 diabetes. Diabetes Technol Ther. 2016;18:252-257.
21.
SeaquistERAndersonJChildsB. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36:1384-1395.
22.
RiddleMCYki-JärvinenHBolliGB. 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 + mealtime insulin (EDITION 1 12-month randomized trial including 6-month extension). Diabetes Obes Metab. 2015;17:835-842.
23.
Yki-JärvinenHBergenstalRMBolliGB. Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension. Diabetes Obes Metab. 2015;17:1142-1149.
24.
JonassenIHavelundSHoeg-JensenTSteensgaardDBWahlundPORibelU. Design of the novel protraction mechanism of insulin degludec, an ultra-long acting basal insulin. Pharm Res. 2012;29:2104-2114.
25.
KeatingGM. Insulin degludec and insulin degludec/insulin aspart: a review of their use in the management of diabetes mellitus. Drugs. 2013;73:575-593.
26.
HeiseTHermanskiLNosekLFeldmanARasmussenSHaahrH. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab. 2012;14:859-864.
27.
HeiseTNosekLBøttcherSGHastrupHHaahrH. Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes. Diabetes Obes Metab. 2012;14:944-950.
28.
HellerSBuseJFisherM. 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;379:1489-1497.
29.
GarberAJKingABDel PratoS; NN1250-3582 (BEGIN BBT2D) Investigators. 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;379:1498-1507.
30.
MathieuCHollanderPMiranda-PalmaB. 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 extension. J Clin Endocrinol Metab. 2013;98:1154-1162.
31.
MeneghiniLAtkinSLGoughSC. 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;36:858-864.
32.
ZinmanBPhilis-TsimikasACariouB. Insulin degludec versus insulin glargine in insulin-naïve patients with type 2 diabetes. Diabetes Care. 2012;35:2464-2471.
33.
OwensDRMatfinGMonnierL. Basal insulin analogues in the management of diabetes mellitus: what progress have we made?Diabetes Metab Res Rev. 2014;30:104-119.
34.
GoughSCBhargavaAJainRMersebachHRasmussenSBergenstalRM. 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;36:2536-2542.
35.
BodeBWChaykinLBSussmanAM. 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;20:785-791.
36.
BerardLMacNeillG. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus. Can J Diabetes. 2015;39:4-9.
37.
CrastoWJarvisJHackettE. Insulin U-500 in severe insulin resistance in type 2 diabetes mellitus. Postgrad Med J. 2009;85:219-222.
38.
de la PeñaARiddleMMorrowLA. Pharmacokinetics and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects. Diabetes Care. 2011;34:2496-2501.
