Insulin Degludec Once Daily Similar to Insulin Glargine
Objective—The 200 units/mL formulation of insulin degludec (IDeg 200 units/mL) contains equal units of insulin in half the volume compared with the 100 units/mL formulation. We compared the efficacy and safety of IDeg 200 units/mL once daily with 100 units/mL insulin glargine (IGlar) in insulin-naïve subjects with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs.
Research Design and Methods—In this 26-week, open-label, treat-to-target trial, subjects (n = 457; mean HbA1c 8.3% [67 mmol/mol], BMI 32.4 kg/m, and fasting plasma glucose [FPG] 9.6 mmol/L [173.2 mg/dL]) were randomized to IDeg 200 units/mL or IGlar, both given once daily in combination with metformin with or without a dipeptidyl peptidase-4 inhibitor. Basal insulin was initiated at 10 units/day and titrated weekly to an FPG target of <5 mmol/L (<90 mg/dL) according to mean prebreakfast self-measured blood glucose values from the preceding 3 days.
Results—By 26 weeks, IDeg reduced HbA1c by 1.30% and was not inferior to IGlar. Mean observed FPG reductions were significantly greater with IDeg than IGlar (−3.7 vs. −3.4 mmol/L [–67 vs. –61 mg/dL]; estimated treatment difference: −0.42 [95% CI −0.78 to −0.06], P = 0.02). Despite this difference, rates of overall confirmed hypoglycemia were not higher with IDeg than with IGlar (1.22 and 1.42 episodes/patient-year, respectively), as were rates of nocturnal confirmed hypoglycemia (0.18 and 0.28 episodes/patient-year, respectively). Mean daily basal insulin dose was significantly lower by 11% with IDeg 200 units/mL compared with IGlar. IDeg was well-tolerated, and the rate of treatment-emergent adverse events was similar across groups.
Conclusions—In this treat-to-target trial in insulin-naïve patients with T2DM, IDeg 200 units/mL improved glycemic control similarly to IGlar with a low risk of hypoglycemia.
Basal insulins are an important treatment option for persons with type 2 diabetes (T2DM), with progressively higher doses of insulin required over the duration of the disease. Moreover, approximately 90% of those with T2DM in the U.S. are overweight, and obese patients often are less sensitive to exogenous insulin and therefore require higher doses to maintain good glycemic control. Globally, approximately 30% of patients with T2DM who use basal insulin require >60 units daily. The use of a highly concentrated formulation of regular insulin, U-500 regular insulin (Humulin R U-500; Eli Lilly and Company, Indianapolis, IN), was originally developed to address high insulin requirements. The frequency of use of U-500 regular insulin increased dramatically by >70% in the U.S. between 2007 and 2008, corresponding to the escalating number of people with T2DM and obesity.
Currently marketed insulin pen devices only allow the administration of a maximum of 80 units per injection, and administration of larger volumes of insulin has typically required the use of a vial and syringe or the addition of a second injection. Very large doses of insulin delivered as a single injection with a syringe may be painful and cause discomfort at the site of injection, and it can be physically challenging to deliver such a large volume smoothly. Together, these limitations highlight the need for an insulin formulation with a higher concentration that allows administration of higher doses of insulin in a single injection.
Insulin degludec (IDeg) is an ultra–long-acting basal insulin that is in clinical development. On subcutaneous injection, IDeg forms soluble multihexamers that slowly dissociate into monomers to produce a flat and consistent insulin action profile, with a duration of action >42 h. To meet the need for higher insulin doses in patients who use prefilled pen devices, a more concentrated 200 units/mL formulation of IDeg was developed at the same time as the 100 units/mL preparation. IDeg 200 units/mL is bioequivalent to IDeg 100 units/mL and demonstrates a similar glucose-lowering effect. Clinical trials comparing IDeg 100 units/mL with insulin glargine (IGlar) at 100 units/mL have demonstrated that IDeg 100 units/mL provides glycemic efficacy similar to that of IGlar, with lower rates of hypoglycemia.
IDeg 200 units/mL contains the same number of units of insulin in half the volume compared with IDeg 100 units/mL and, when administered in the new FlexTouch pen device, can deliver as much as 160 units of insulin in a single injection. There is no dose correction or calculation necessary, because the FlexTouch pen internally corrects for the 200 units/mL concentration. Thus only the injected volume of a given dose of insulin differs between the 200 units/mL pen device and other devices. This eliminates any potential dose confusion when changing between currently available 100 units/mL basal insulin products and the possibility of mistakenly interchanging IDeg 100 units/mL and 200 units/mL insulin pens (on their approval by the U.S. Food and Drug Administration).
The purpose of this study was to compare efficacy and safety between IDeg 200 units/mL and IGlar, both administered once daily in combination with metformin with or without a dipeptidyl peptidase-4 (DPP-4) inhibitor, in insulin-naïve patients with T2DM requiring an intensification of treatment.
Abstract and Introduction
Abstract
Objective—The 200 units/mL formulation of insulin degludec (IDeg 200 units/mL) contains equal units of insulin in half the volume compared with the 100 units/mL formulation. We compared the efficacy and safety of IDeg 200 units/mL once daily with 100 units/mL insulin glargine (IGlar) in insulin-naïve subjects with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs.
Research Design and Methods—In this 26-week, open-label, treat-to-target trial, subjects (n = 457; mean HbA1c 8.3% [67 mmol/mol], BMI 32.4 kg/m, and fasting plasma glucose [FPG] 9.6 mmol/L [173.2 mg/dL]) were randomized to IDeg 200 units/mL or IGlar, both given once daily in combination with metformin with or without a dipeptidyl peptidase-4 inhibitor. Basal insulin was initiated at 10 units/day and titrated weekly to an FPG target of <5 mmol/L (<90 mg/dL) according to mean prebreakfast self-measured blood glucose values from the preceding 3 days.
Results—By 26 weeks, IDeg reduced HbA1c by 1.30% and was not inferior to IGlar. Mean observed FPG reductions were significantly greater with IDeg than IGlar (−3.7 vs. −3.4 mmol/L [–67 vs. –61 mg/dL]; estimated treatment difference: −0.42 [95% CI −0.78 to −0.06], P = 0.02). Despite this difference, rates of overall confirmed hypoglycemia were not higher with IDeg than with IGlar (1.22 and 1.42 episodes/patient-year, respectively), as were rates of nocturnal confirmed hypoglycemia (0.18 and 0.28 episodes/patient-year, respectively). Mean daily basal insulin dose was significantly lower by 11% with IDeg 200 units/mL compared with IGlar. IDeg was well-tolerated, and the rate of treatment-emergent adverse events was similar across groups.
Conclusions—In this treat-to-target trial in insulin-naïve patients with T2DM, IDeg 200 units/mL improved glycemic control similarly to IGlar with a low risk of hypoglycemia.
Introduction
Basal insulins are an important treatment option for persons with type 2 diabetes (T2DM), with progressively higher doses of insulin required over the duration of the disease. Moreover, approximately 90% of those with T2DM in the U.S. are overweight, and obese patients often are less sensitive to exogenous insulin and therefore require higher doses to maintain good glycemic control. Globally, approximately 30% of patients with T2DM who use basal insulin require >60 units daily. The use of a highly concentrated formulation of regular insulin, U-500 regular insulin (Humulin R U-500; Eli Lilly and Company, Indianapolis, IN), was originally developed to address high insulin requirements. The frequency of use of U-500 regular insulin increased dramatically by >70% in the U.S. between 2007 and 2008, corresponding to the escalating number of people with T2DM and obesity.
Currently marketed insulin pen devices only allow the administration of a maximum of 80 units per injection, and administration of larger volumes of insulin has typically required the use of a vial and syringe or the addition of a second injection. Very large doses of insulin delivered as a single injection with a syringe may be painful and cause discomfort at the site of injection, and it can be physically challenging to deliver such a large volume smoothly. Together, these limitations highlight the need for an insulin formulation with a higher concentration that allows administration of higher doses of insulin in a single injection.
Insulin degludec (IDeg) is an ultra–long-acting basal insulin that is in clinical development. On subcutaneous injection, IDeg forms soluble multihexamers that slowly dissociate into monomers to produce a flat and consistent insulin action profile, with a duration of action >42 h. To meet the need for higher insulin doses in patients who use prefilled pen devices, a more concentrated 200 units/mL formulation of IDeg was developed at the same time as the 100 units/mL preparation. IDeg 200 units/mL is bioequivalent to IDeg 100 units/mL and demonstrates a similar glucose-lowering effect. Clinical trials comparing IDeg 100 units/mL with insulin glargine (IGlar) at 100 units/mL have demonstrated that IDeg 100 units/mL provides glycemic efficacy similar to that of IGlar, with lower rates of hypoglycemia.
IDeg 200 units/mL contains the same number of units of insulin in half the volume compared with IDeg 100 units/mL and, when administered in the new FlexTouch pen device, can deliver as much as 160 units of insulin in a single injection. There is no dose correction or calculation necessary, because the FlexTouch pen internally corrects for the 200 units/mL concentration. Thus only the injected volume of a given dose of insulin differs between the 200 units/mL pen device and other devices. This eliminates any potential dose confusion when changing between currently available 100 units/mL basal insulin products and the possibility of mistakenly interchanging IDeg 100 units/mL and 200 units/mL insulin pens (on their approval by the U.S. Food and Drug Administration).
The purpose of this study was to compare efficacy and safety between IDeg 200 units/mL and IGlar, both administered once daily in combination with metformin with or without a dipeptidyl peptidase-4 (DPP-4) inhibitor, in insulin-naïve patients with T2DM requiring an intensification of treatment.