For adult patients with type 2 diabetes

Levemir® once dailya added to metformin + Victoza® (liraglutide [rDNA origin] injection) helped achieve treatment goals1,b

Significant reductions in A1C and FPG over 26 weeks1

Study design1,2

  • Main treatment period lasted 26 weeks
  • Patients with A1C ≥7% were randomized 1:1 to either
    • Metformin + Victoza® 1.8 mg (n=161)
    • Metformin + Victoza® 1.8 mg + Levemir® starting at 10 units/day (n=162)

This was a multinational, open-label study of 988 insulin-naïve adults with type 2 diabetes (18 to 80 years) who were uncontrolled on metformin ≥1500 mg/day +/– SU. All patients underwent a 12-week run-in with metformin and Victoza® once daily, titrated to 1.8 mg. At the end of the run-in period, if patients achieved A1C <7%, they continued treatment in a nonrandomized, observational arm (50% of patients from run-in). If A1C was ≥7% at the end of run-in, patients were randomized to 26 weeks of once-daily Levemir® as add-on therapy or to continued, unchanged treatment with Victoza® 1.8 mg and metformin.2

aLevemir® can be dosed once or twice daily.

bVictoza® is a GLP-1 receptor agonist.

 

In the metformin + Victoza® + Levemir® arm1,2,c

Results of study with Levemir® once daily added to metformin + Victoza®

cP<0.0001 was vs metformin + Victoza® group. Results from the metformin + Victoza® arm not shown.


 

  • 43% of patients in the metformin + Victoza® + Levemir® arm reached goal of A1C<7%1,2
 

Hypoglycemia

This study also showed low rates of hypoglycemia with metformin + Victoza® + Levemir® in adults with type 2 diabetes


 

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

  • 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. Needles, insulin pens, or syringes should never be shared.

Selected Important Safety Information

WARNING: RISK OF THYROID C-CELL TUMORS

Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be ruled out by clinical or nonclinical studies. Victoza® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Based on the findings in rodents, monitoring with serum calcitonin or thyroid ultrasound was performed during clinical trials, but this may have increased the number of unnecessary thyroid surgeries. It is unknown whether monitoring with serum calcitonin or thyroid ultrasound will mitigate human risk of thyroid C-cell tumors. Patients should be counseled regarding the risk and symptoms of thyroid tumors.

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

  • 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. Needles, insulin pens, or syringes should never be shared.

  • 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 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.

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.

Please click here for Prescribing Information.

 

Victoza® (liraglutide [rDNA origin] injection) Indications and Usage

  • Victoza® (liraglutide [rDNA origin] injection) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Important Limitations of Use

  • Because of the uncertain relevance of the rodent thyroid C-cell tumor findings to humans, prescribe Victoza® only to patients for whom the potential benefits are considered to outweigh the potential risk. Victoza® is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise
  • Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been observed in patients treated with Victoza®. Victoza® has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using Victoza®. Other antidiabetic therapies should be considered in patients with a history of pancreatitis
  • Victoza® is not a substitute for insulin. Victoza® should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings
  • Victoza® has not been studied in combination with prandial insulin

Important Safety Information

WARNING: RISK OF THYROID C-CELL TUMORS

Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be ruled out by clinical or nonclinical studies. Victoza® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Based on the findings in rodents, monitoring with serum calcitonin or thyroid ultrasound was performed during clinical trials, but this may have increased the number of unnecessary thyroid surgeries. It is unknown whether monitoring with serum calcitonin or thyroid ultrasound will mitigate human risk of thyroid C-cell tumors. Patients should be counseled regarding the risk and symptoms of thyroid tumors.

Contraindications

  • Do not use in patients with a prior serious hypersensitivity reaction to Victoza® or to any of the product components

Warnings and Precautions

  • Pancreatitis: Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been observed in patients treated with Victoza®. After initiation of Victoza®, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, Victoza® should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confirmed, Victoza® should not be restarted. Consider antidiabetic therapies other than Victoza® in patients with a history of pancreatitis
  • Use with Medications Known to Cause Hypoglycemia: When Victoza® is used with an insulin secretagogue (e.g. a sulfonylurea) or insulin serious hypoglycemia can occur. Consider lowering the dose of the insulin secretagogue or insulin to reduce the risk of hypoglycemia
  • Renal Impairment: Renal impairment has been reported postmarketing, usually in association with nausea, vomiting, diarrhea, or dehydration, which may sometimes require hemodialysis. Use caution when initiating or escalating doses of Victoza® in patients with renal impairment
  • Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g. anaphylaxis and angioedema) have been reported during postmarketing use of Victoza®. If symptoms of hypersensitivity reactions occur, patients must stop taking Victoza® and seek medical advice promptly
  • Macrovascular Outcomes: There have been no studies establishing conclusive evidence of macrovascular risk reduction with Victoza® or any other antidiabetic drug

Adverse Events

  • The most common adverse reactions, reported in ≥5% of patients treated with Victoza® and more commonly than in patients treated with placebo, are headache, nausea, diarrhea, dyspepsia, constipation and anti-liraglutide antibody formation. Immunogenicity-related events, including urticaria, were more common among Victoza®-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials

Use in Specific Populations

  • Victoza® has not been studied in type 2 diabetes patients below 18 years of age and is not recommended for use in pediatric patients

  • There is limited data in patients with renal or hepatic impairment

Please click here for Prescribing Information.

 

References

  1. Levemir [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2013.
  2. DeVries JH, Bain SC, Rodbard HW, et al; Liraglutide-Detemir Study Group. Sequential intensification of metformin treatment in type 2 diabetes with liraglutide followed by randomized addition of basal insulin promoted by A1C targets. Diabetes Care. 2012;35(7):1446-1454.