Levemir® — the first basal insulin analog with Pregnancy Category B classification.1

Levemir® is the first FDA-approved basal insulin analog with Pregnancy Category B classification.

In a randomized, controlled clinical trial1:

  • Pregnant women with type 1 diabetes (n=310) were treated with either Levemir® (n=152) or NPH insulin (n=158) in a basal-bolus regimena
  • Women were randomized either as pregnant or planning pregnancy; those who where randomized as pregnant were between weeks 8 and 12 of gestationb
  • Approximately one-half of the study participants in each arm were randomized as pregnant and were exposed to NPH insulin or other insulins prior to conception and in the first 8 weeks of gestation
  • According to pretrial insulin regimen:
    • Levemir® was administered once or twice daily
    • NPH was administered once, twice, or 3 times a day
 

Comparable A1C reductions vs NPH insulin1,2

Reductions in A1C during gestation

Comparison of Levemir® vs. NPH insulin reductions in A1C during gestation

An open-label, randomized, parallel-group, multinational study in women with type 1 diabetes who were on insulin for at least 12 months before randomization and who were planning to become pregnant or already pregnant at gestational weeks (GWs) 8 to 12. Patients could enroll in the study with intention to become pregnant. Patients were withdrawn from the trial if they did not become pregnant within 1 year. Patients were separated at randomization as pregnant and nonpregnant and all were required to have A1C ≤8% at confirmation of pregnancy. Patients were randomized 1:1 to Levemir® (n=152) or NPH insulin (n=158). Both groups used NovoLog® (insulin aspart [rDNA origin] injection) as mealtime insulin. Approximately 50% of the women also received Levemir® or NPH insulin prior to conception and in the first 8 weeks of gestation. Regimen was followed from randomization until termination/6 weeks postdelivery.2

Adapted from Mathiesen et al, 2012.2



 

Similar rates of hypoglycemia vs NPH insulin1,c

Rates of severe hypoglycemia

Chart comparing Levemir® rates of severe hypoglycemia vs. NPH insulin
  • Minor hypoglycemia rates were comparable (104.4 events per patient/year for the Levemir® group, 101.0 events per patient/year for the NPH insulin group)

 

aBoth groups used NovoLog® (insulin aspart [rDNA origin] injection) as mealtime insulin.

bPatients were withdrawn from the trial if they did not become pregnant within 1 year.

cNon-severe=PG <56 mg/dL (BG <50 mg/dL) with or without symptoms (patient able to self-treat). Severe=PG <56 mg/dL (BG <50 mg/dL) with symptoms consistent with hypoglycemia or reversal of symptoms after food intake, glucagon, or intravenous glucose (patient unable to self-treat).

 

“No difference in pregnancy outcomes or the health of the fetus and newborn were seen with Levemir® use”1


 

Related Safety 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. Levemir [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2015.
  2. Mathiesen ER, Hod M, Ivanisevic M, et al; Detemir in Pregnancy Study Group. Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes. Diabetes Care. 2012;35(10):2012-2017.