Sherri, who has type 2 diabetes, says NovoLog® is her type for mealtime control she can manage

Rates of hypoglycemia

Low Rates of hypoglycemia in the FullSTEP® study1

In the FullSTEP® study, patients uncontrolled on basal insulin with or without OADs were randomized to either a stepwise approach or a full basal-bolus dosing arm. In the stepwise arm, patients added NovoLog® to their basal insulin at the patient-perceived largest meal of the day. After 11 weeks and 22 weeks, additional doses of NovoLog® were added, if A1C was ≥ 7%, to the next largest patient-perceived largest meals. In the full basal-bolus arm, NovoLog® was added at all 3 main meals from the start. The study found that there were significantly fewer hypoglycemic events with a stepwise regimen vs full basal-bolus.

 

Significantly fewer hypoglycemic events with a stepwise regimen vs full basal-bolus.

Chart showing hypoglycemic events reduction with a stepwise regimen vs full basal bolus.


Rodbard et al (FullSTEP®)
, a randomized, open-label, multinational, non-inferiority, 32-week treat-to-target trial. Patients with type 2 diabetes inadequately controlled on basal insulin with or without OADs were randomized to either a stepwise arm or full basal-bolus arm. In the stepwise arm (n=201), NovoLog® (insulin aspart [rDNA origin] injection) was added to basal insulin at the patient-perceived largest meal initially. Additional doses were added to the next largest patient-perceived largest meal at weeks 11 and 22 if A1C ≥7%. In the full basal-bolus arm (n=200), NovoLog® was added at all 3 main meals from the start. Patients in both arms self-titrated NovoLog® daily based on the previous day's premeal or bedtime self-measured plasma glucose levels.

Adapted from Rodbard et al 2002.

 

Hypoglycemic rates in the stepwise arm did NOT reach the level of the full basal-bolus group-even at study end, when more than one-third of patients were on 3 doses per day of NovoLog®.

"Stepwise prandial insulin intensification provides glycaemic control non-inferior to a full basal-bolus regimen after 32 weeks, with significantly lower hypoglycaemia risk..."

— HW Rodbard, MD

 



 

Efficacy and FullSTEP®

The FullSTEP® study also examined the effects on A1C levels.


 




Low rates of hypoglycemia in the 4-T study2

Treating to Target in Type 2 Diabetes (4-T), tried a second approach to intensifying to basal–bolus therapy: with basal insulin continued, 3 mealtime injections were added at once. Dosing began at 10% of the daily basal dose, between 4 and 6 units per meal. These patients were followed for 3 years and saw an A1C reduction of 1.2%. Sixty-three percent achieved the A1C goal of ≤7%.

Results:
Low rates of hypoglycemia were seen over 3 years in patients intensifying to basal-bolus therapy with NovoLog®.2

 

Hypoglycemic events2a (number/patient/year)

Chart showing number of hypoglycemic patient per year

A 3-year, multicenter, randomized, treat-to-target study of 708 insulin-naïve patients with type 2 diabetes. A total of 234 patients were randomized to Levemir® and were intensified with NovoLog® if A1C was >10% after 1 measurement or ≥8% for 2 consecutive measurements at or after 24 weeks, or if A1C was >6.5% at 1 year. At study end, 82% of patients had been intensified with NovoLog®. The results of this arm of the study are shown here. In addition, 239 patients were randomized to NovoLog® and 235 patients were randomized to biphasic insulin aspart 30 (results not shown). All insulin was delivered by FlexPen®.2,3 Data is representative of all patients in the Levemir®- initiated arm.

aCalculation based on median. Grade 2 (minor) symptoms with blood glucose <56 mg/dL; Grade 3 (major) required third-party assistance.

Adapted from Holman et al 2009.2


 

Efficacy and 4-T

The 4-T study also examined effects on A1C levels.


 


 

Rates of hypoglycemia vs insulin glulisine4

A pump study in type 1 diabetes compared blood glucose profiles with NovoLog® and the rapid-acting insulin analogs, insulin lispro and insulin glulisine, over approximately 10 months. According to this study’s crossover design, each subject used each insulin over a 13-week period, in 1 of 3 sequences.

Results:

  • Lower monthly rate of unexplained hyperglycemia compared with insulin glulisine (P<0.001)
  • Lower monthly rate of perceived infusion set occlusion compared with insulin glulisine (P=0.02)
  • The percentage of patients with ≥1 unexplained hyperglycemic event and/or perceived infusion set occlusion with NovoLog® vs insulin glulisine was not statistically significant (62.1 vs 68.4, respectively)

 

NovoLog® in a pump: Monthly rate of unexplained hyperglycemia or perceived infusion set occlusion4

Chart showing monthly rate of unexpected hyperglycemia or perceived infusion set occlusion

Study design: A 39-week, randomized, controlled, multinational, open-label, 3-way crossover study enrolling 256 adult patients with type 1 diabetes assigned to 1 of 3 treatment groups (glulisine–NovoLog®–lispro; NovoLog®–lispro–glulisine; lispro–glulisine– NovoLog®) and then “crossed over” (13 weeks per each intervention).4


 

Efficacy vs insulin glulisine

The same study also examined PPG levels vs insulin glulisine.


 



 

Rates of hypoglycemia vs insulin lispro5

Shown are patient-reported hypoglycemic episodes per patient per month for NovoLog® and insulin lispro, in 2 periods: a 4-week run-in period and a 12-week maintenance period.

Results:
No patients in the NovoLog® or lispro group reported a major hypoglycemic event (defined as requiring IV glucose).

 

Rate of hypoglycemic episodes6

Chart comparing rate of hypokalemic episodes novolog vs insulin lispro


Dose-adjustment period was 4 weeks. Maintenance period was 12 weeks.

A 16-week, open-label, randomized, parallel-group study enrolling 146 patients with type 1 diabetes for at least 12 months. Patients were randomized to receive NovoLog®, insulin lispro, or buffered regular insulin as part of continuous subcutaneous insulin infusion (CSII) therapy.

Buffered regular insulin is no longer manufactured in the United States.

Adapted from Bode et al, 2002.5


 

Efficacy vs insulin lispro

The same study also examined PPG levels vs insulin lispro


 


Related Safety Topics:

Selected Important Safety Information

Contraindications

  • NovoLog® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® or one of its excipients.

Warnings and Precautions

  • Never Share a NovoLog® FlexPen, NovoLog® FlexTouch®, PenFill® Cartridge, or PenFill® Cartridge Device Between Patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.
  • Administration: NovoLog® should generally be given immediately (within 5-10 minutes) prior to the start of a meal. Any change of insulin dose should be made cautiously and only under medical supervision. Changing from one insulin product to another or changing the insulin strength may result in the need for a change in dosage. As with all insulin preparations, the time course of action of NovoLog® may vary in different individuals or at different times in the same individual and is dependent on many conditions, including injection site, local blood supply, temperature, and level of physical activity. NovoLog® should be used with a longer-acting insulin.

Selected Important Safety Information

Contraindications

  • Levemir® is contraindicated in patients with hypersensitivity to Levemir® or any of its excipients.

Warnings and Precautions

  • Never Share a Levemir® FlexTouch® Between Patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.
  • Dosage adjustment and monitoring: Monitor blood glucose in all patients treated with insulin. Insulin regimens should be modified cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment of concomitant anti-diabetic treatment.
  • Administration: Do not dilute or mix with any other insulin or solution. Do not administer subcutaneously via an insulin pump, intramuscularly, or intravenously because severe hypoglycemia can occur. 

NovoLog® (insulin aspart [rDNA origin] injection) Indications and Usage

  • NovoLog® (insulin aspart [rDNA origin] injection) is an insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus.

Important Safety Information

Contraindications

  • NovoLog® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® or one of its excipients.

Warnings and Precautions

  • Never Share a NovoLog® FlexPen, NovoLog® FlexTouch®, PenFill® Cartridge, or PenFill® Cartridge Device Between Patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.
  • Administration: NovoLog® should generally be given immediately (within 5-10 minutes) prior to the start of a meal. Any change of insulin dose should be made cautiously and only under medical supervision. Changing from one insulin product to another or changing the insulin strength may result in the need for a change in dosage. As with all insulin preparations, the time course of action of NovoLog® may vary in different individuals or at different times in the same individual and is dependent on many conditions, including injection site, local blood supply, temperature, and level of physical activity. NovoLog® should be used with a longer-acting insulin.
  • Hypoglycemia: Hypoglycemia is the most common adverse effect of insulin therapy. The timing of hypoglycemia may reflect the time-action profile of the insulin formulation. Glucose monitoring is recommended for all patients with diabetes and is particularly important for patients using external pump infusion therapy. Any change of insulin dose should be made cautiously and only under medical supervision.
  • Hypokalemia: Insulin, particularly when given intravenously or in settings of poor glycemic control, can cause hypokalemia. Use caution in patients predisposed to hypokalemia.
  • Renal and Hepatic Impairment: Like all insulins, NovoLog® requirements may be reduced in patients with renal impairment or hepatic impairment.
  • Hypersensitivity and Allergic Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulin products, including NovoLog®
  • Continuous Subcutaneous Insulin Infusion by External Pump: When used in an external subcutaneous insulin infusion pump, NovoLog® should not be mixed with any other insulin or diluent.
  • Fluid retention and heart failure with concomitant use of PPAR-gamma agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including NovoLog®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.

Adverse Reactions

  • Adverse reactions observed with NovoLog® include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus.

Use in Specific Populations

  • NovoLog® has not been studied in children with type 2 diabetes or in children with type 1 diabetes who are younger than 2 years of age.
  • The background risk of birth defects, pregnancy loss, or other adverse events that exists for all pregnancies is increased in pregnancies complicated by hyperglycemia.

Please click here for Prescribing Information.

 

Levemir® (insulin detemir [rDNA origin] injection) Indications and Usage

  • Levemir® (insulin detemir [rDNA origin] injection) is indicated to improve glycemic control in adults and children with diabetes mellitus.

Important Limitations of Use

  • Levemir® is not recommended for the treatment of diabetic ketoacidosis. Intravenous rapid-acting or short-acting insulin is the preferred treatment for this condition.

Important Safety Information

Contraindications

  • Levemir® is contraindicated in patients with hypersensitivity to Levemir® or any of its excipients.

Warnings and Precautions

  • Never Share a Levemir® FlexTouch® Between Patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.
  • Dosage adjustment and monitoring: Monitor blood glucose in all patients treated with insulin. Insulin regimens should be modified cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in the insulin dose or an adjustment of concomitant anti-diabetic treatment.
  • Administration: Do not dilute or mix with any other insulin or solution. Do not administer subcutaneously via an insulin pump, intramuscularly, or intravenously because severe hypoglycemia can occur.

  • Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin therapy and may be life-threatening. When a GLP-1 receptor agonist is used in combination with Levemir®, the Levemir® dose may need to be lowered or more conservatively titrated to minimize the risk of hypoglycemia.

  • Hypersensitivity and allergic reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including Levemir®.

  • Renal and hepatic impairment: Careful glucose monitoring and dose adjustments of insulin, including Levemir®, may be necessary in patients with renal or hepatic impairment.
  • Drug interactions: Some medications may alter insulin requirements and subsequently increase the risk for hypoglycemia or hyperglycemia.
  • Fluid retention and heart failure with concomitant use of PPAR-gamma agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including Levemir®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.

Adverse Reactions

  • Adverse reactions associated with Levemir® include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, rash, pruritus, and if taken with a GLP-1 receptor agonist, diarrhea.

Use in Specific Populations

  • Levemir® has not been studied in children with type 2 diabetes or in children with type 1 diabetes who are younger than 2 years of age.

  • The background risk of birth defects, pregnancy loss, or other adverse events that exists for all pregnancies is increased in pregnancies complicated by hyperglycemia.

Please click here for Prescribing Information.

 

References

  1. Rodbard HW, Visco VE, Andersen H, Hiort LC, Shu DHW. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): a randomised, treat-to-target clinical trial. Lancet Diabetes Endocrinol. 2014;2:30-37.
  2. Holman RR, Farmer AJ, Davies MJ, et al; for the 4-T Study Group. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736-1747.
  3. Holman RR, Thorne KI, Farmer AJ, et al; for the 4-T Study Group. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007;357(17):1716-1730.
  4. van Bon AC, Bode BW, Sert-Langeron C, DeVries JH, Charpentier G. Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial. Diabetes Technol Ther. 2011;13(6):607-614.
  5. Bode B, Weinstein R, Bell D, et al. Comparison of insulin aspart with buffered regular insulin and insulin lispro in continuous subcutaneous insulin infusion: a randomized study in type 1 diabetes. Diabetes Care. 2002;25(3):439-444.
  6. Data on file. Novo Nordisk, Inc., Plainsboro, NJ.