Abstract and Introduction
Abstract
Objective: The purpose of the present study was to provide clinical data on the efficacy and safety of insulin degludec (IDeg) 200 U/mL compared with IDeg 100 U/mL in patients with type 2 diabetes mellitus (T2DM) currently treated with basal insulin in combination with oral antidiabetic drugs.
Methods: In this 22-week, treat-to-target trial, eligible adult patients with T2DM were randomized 1:1 to IDeg 200 or IDeg 100 U/mL once daily (OD) (n = 186 and 187, respectively). The starting insulin dose was based on a 1:1 transfer of the total prerandomization basal insulin dose. The primary endpoint was change (%) from baseline in glycosylated hemoglobin A1C (A1C) after 22 weeks of treatment.
Results: A total of 373 subjects (mean age 59.8 years, A1C 8.2%, fasting plasma glucose 149.6 mg/dL [8.3 mmol/L], body mass index 33.3 kg/m2) were randomized. A1C reduction with IDeg 200 U/mL was noninferior to that of IDeg 100 U/mL (IDeg 200 U/mL – IDeg 100 U/mL estimated treatment difference: −0.11%, 95% confidence interval (CI): −0.28 to 0.05). Rates of overall confirmed hypoglycemia were low and similar between both formulations (5.17 and 5.66 events/patient-year of exposure [PYE] for IDeg 200 and 100 U/mL, respectively). Similarly, the rates of nocturnal confirmed hypoglycemia were low (1.27 and 1.70 events/PYE for 200 and 100 U/mL). In general, both IDeg formulations were well tolerated (respective rates of adverse events: 4.16 and 3.00 events/PYE for 200 and 100 U/mL).
Conclusion: The 200 and 100 U/mL formulations of IDeg provide comparable and effective levels of glycemic control with similar, low rates of overall confirmed and nocturnal confirmed hypoglycemia.
Introduction
Obesity and its associated insulin resistance have contributed not only to increased prevalence of type 2 diabetes mellitus (T2DM) but also to a rise in the insulin needs of insulin-requiring patients with T2DM.[1] According to the 2011 National Diabetes Statistics, 12 to 14% of adults diagnosed with T2DM received treatment with insulin either as monotherapy or in combination with oral antidiabetic drugs (OADs).[2]
Concentrated human regular insulin (500 U/mL or U500) was developed to address high insulin needs in patients with diabetes. Rigorous clinical data from randomized controlled trials investigating U500 are lacking, and its clinical use is based primarily on retrospective-type case series.[1] As the only available concentrated insulin currently on the market, the use of U500 regular insulin can be challenging. U500 insulin requires the use of conventional vials and syringes calibrated for the 100 U/mL concentration, which can cause errors in dosing and warrants close patient monitoring by healthcare professionals due to potential prescribing errors and hypoglycemia.[3]
Insulin degludec (IDeg), a novel basal insulin with an ultra-long duration of action, approved in the European Union, Japan (only the 100 U/mL formulation), Mexico, and several other countries, was developed as 2 different formulations: a 100 U/mL formulation and a 200 U/mL formulation. IDeg 200 and 100 U/mL have previously been shown to have similar glucose-lowering effects and durations of action based on area under the curve (AUC) analysis, and the bioequivalence of both formulations has been established based on AUC and maximum concentration (Cmax) values.[4] In phase 3 clinical trials, either formulation, when compared to insulin glargine, consistently demonstrated a lower rate of hypoglycemia, particularly nocturnal hypoglycemia, and lower fasting plasma glucose (FPG) at similar levels of glycemic control.[5–9] IDeg 200 U/mL was developed to address the increasing insulin requirements of patients with diabetes. Using the IDeg 200 U/mL formulation, which will be available only in a prefilled pen device, insulin doses can be administered in half the volume compared to the 100 U/mL formulation. A smaller volume of insulin is likely to benefit patients with any insulin dose requirement but particularly for those patients with large insulin requirements (>80 U/injection). Consequently, the 200 U/mL formulation of IDeg provides patients with the ability to administer their required insulin dose in 1 injection (up to 160 U) instead of multiple injections.
IDeg 200 and 100 U/mL are both administered in the novel, prefilled FlexTouch® pen (Novo Nordisk A/S, Bagsværd, Denmark). The dose dial window on the FlexTouch® pen displays the selected dose in insulin units (U) for both formulations. Thus, FlexTouch® delivers the selected dose by dialing to the value displayed in the dose unit window. No dose correction or calculation is necessary.
The purpose of the present study was to provide additional clinical data on the efficacy and safety of IDeg 200 U/mL in a head-to-head comparison with IDeg 100 U/mL in patients with T2DM currently treated with basal insulin in combination with OAD therapy.
Endocr Pract. 2014;20(8):785-791. © 2014 American Association of Clinical Endocrinologists
