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 Patients were withdrawn from the trial if they did not become pregnant within 1 year.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 injection) 100 U/mL 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 injection) 100 U/mL 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bPatients were withdrawn from the trial if they did not become pregnant within 1 year.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. Patients using NovoLog® vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 
  • Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made cautiously under close medical supervision and the frequency of blood glucose monitoring should be increased.

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 injection) 100 U/mL Indications and Usage

  • NovoLog® (insulin aspart injection) 100 U/mL 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. Patients using NovoLog® vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 
  • Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made cautiously under close medical supervision and the frequency of blood glucose monitoring should be increased. 
  • 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. 
  • To avoid medication errors and accidental mix-ups between NovoLog® and other insulin products, instruct patients to always check the insulin label before injection. 
  • Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulin products, including NovoLog®
  • As with all insulins, NovoLog® use can lead to life-threatening hypokalemia, which then may cause respiratory paralysis, ventricular arrhythmia, and death.  Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
  • 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. 
  • Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Patients using insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure. 

NovoLog® continuous subcutaneous infusion route (insulin pump): Do not mix NovoLog® with any other insulin or diluent.

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. 
  • Like all insulins, NovoLog® requirements may be reduced in patients with renal impairment or hepatic impairment. These patients may require more frequent blood glucose monitoring and dose adjustments. 

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.