For patients with type 2 diabetes

Levemir® demonstrated significantly less weight gain vs insulin glargine1,2

Results from trial study comparing Levemir® weight gain with Insulin glargine

A 52-week, multinational, open-label, parallel-group, treat-to-target trial using a noninferiority design. Subjects diagnosed with type 2 diabetes ≥12 months on any oral antidiabetic drug (OAD) therapy or on any insulin regimen with or without OAD therapy for >4 months were randomized 2:1 to the Levemir® and insulin glargine treatment arms, respectively. A total of 323 patients were randomized; 257 completed the study. In both treatment groups, insulin aspart was administered as a mealtime insulin. Insulin glargine was dosed once daily. Levemir® was initiated once daily and study protocol recommended that Levemir® patients be switched to twice-daily injections if average predinner glucose was >108 mg/dL. 42.8% of patients on Levemir® remained on once-daily dosing throughout the course of the study.2

Adapted from Hollander et al, 2008.2


Whether these observed weight results represent true effects of Levemir® and other therapies are not known since the trial was not blinded, and the protocol (eg, diet and exercise instructions and monitoring) was not specifically directed at exploring hypotheses related to weight effects of the treatments evaluated. The clinical significance of these observed effects has not been established.

 
  • In another study, patients taking Levemir® experienced 23% less weight gain vs patients taking insulin glargine (+6.6 lb vs +8.6 lb, respectively; P=0.01)1
 

Patients with higher baseline BMI experienced less weight gain3

Results from the 70-90 mg/dL FPG target group3

Trial study results showing patients with higher BMI experienced less weight gain

Results from a 20-week randomized, controlled, multicenter, open-label, parallel-group, treat-to-target trial using a physician-directed self-titration algorithm in insulin-naïve patients with type 2 diabetes. A1C ≥7% and ≤9% on OAD therapy randomized to Levemir® and OAD (1:1) to 2 different FPG titration targets (70-90 mg/dL [n=122] or 80-110 mg/dL [n=122]). Subgroup with BMI >40 not shown.3

Adapted from Blonde et al, 2009.3


Whether these observed weight results represent true effects of Levemir® and other therapies are not known since the trial was not blinded, and the protocol (eg, diet and exercise instructions and monitoring) was not specifically directed at exploring hypotheses related to weight effects of the treatments evaluated. The clinical significance of these observed effects has not been established.


 

Levemir® once dailya demonstrated significantly less weight gain in patients vs NPH insulin4

Significantly less weight gain4

Chart comparing Levemir® weight gain vs. NPH insulin

Hermansen et al, a 24-week, randomized, multicenter, open-label, parallel-group, treat-to-target trial in insulin-naïve patients with type 2 diabetes currently taking 1 or 2 OADs. Patients were randomized to either twice-daily Levemir® (n=227) or NPH insulin (n=225).4

Adapted from Hermansen et al.4

aLevemir® can be dosed once or twice daily.


Whether these observed weight results represent true effects of Levemir® and other therapies are not known since the trial was not blinded, and the protocol (eg, diet and exercise instructions and monitoring) was not specifically directed at exploring hypotheses related to weight effects of the treatments evaluated. The clinical significance of these observed effects has not been established.


 

A significant weight difference with Levemir® across multiple studies5-7

  • 45% less weight gain after 26 weeks in Haak et al
    (Levemir®: +2.2 lb; NPH insulin: +4.0 lb [P=0.017])b
  • 57% less weight gain after 20 weeks in Philis-Tsimikas et al
    (Levemir®: +1.5 lb; NPH insulin: +3.5 lb [P=0.005])c
  • 56% less weight gain after 22 weeks in Rašlová et al
    (Levemir®: +1.1 lb; NPH insulin: +2.5 lb [P=0.038])d

bHaak et al, a 26-week, randomized, multicenter, open-label, parallel-group trial in patients with type 2 diabetes of duration >12 months and insulin treatment duration of at least 2 months. Patients were randomized 2:1 to either once- or twice-daily Levemir® (n=341) or NPH insulin (n=164) as part of basal-bolus therapy with NovoLog®.5

cPhilis-Tsimikas et al, a 20-week, randomized, multicenter, open-label, parallel-group trial in insulin-naïve type 2 diabetes patients who were uncontrolled on 1 or 2 OADs. Patients were randomized to once-dailya Levemir® AM administration (n=168), once-dailya Levemir® PM administration (n=170), or NPH insulin (n=166).6

dRašlová et al, a 22-week, randomized, multicenter, open-label, parallel-group trial in patients with type 2 diabetes. Patients were randomized to 1 of 2 basal-bolus regimens: once- or twice-daily Levemir® plus NovoLog® (n=195) or NPH insulin plus regular human insulin (n=199).7

 

Related Efficacy Topics:

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. 

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.

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.

 

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.

 

References
  1. Rosenstock J, Davies M, Home PD, Larsen J, Koenen C, Schernthaner G. 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(3):408-416.
  2. Hollander P, Cooper J, Bregnhøj J, Pedersen CB. A 52-week, multinational, open-label, parallel-group, noninferiority, treat-to-target trial comparing insulin detemir with insulin glargine in a basal-bolus regimen with mealtime insulin aspart in patients with type 2 diabetes. Clin Ther. 2008,20(11):1976-1987.
  3. Blonde L, Merilainen M, Karwe V, Raskin P; TITRATE Study Group. Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets—the TITRATE study. Diabetes Obes Metab. 2009;116:623-631.
  4. 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-naïve people with type 2 diabetes. Diabetes Care. 2006;29(6):1269-1274.
  5. Haak T, Tiengo A, Draeger E, et al. Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes. Diabetes Obes Metab. 2005;7:56-64.
  6. Philis-Tsimikas A, Charpentier C, 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(10):1569-1581.
  7. Rašlová K, Bogoev M, Raz I, et al. Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes. Diabetes Res Clin Pract. 2004;66:193-201.