For patients with type 2 diabetes

Levemir® once dailya had low rates of hypoglycemia1

In TITRATE™, a 20-week randomized clinical trial1:

Low rates of hypoglycemia in patients with type 2 diabetes being treated to reach A1C goal <7%1,b

The TITRATE™ clinical trial showed low rates of hypoglycemia in adult patients with type 2 diabetes

FPG=fasting plasma glucose.

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 oral antidiabetic drug (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]). At study end, in the 80-110 mg/dL group, 55% of patients achieved goal (A1C ≤7%) with a mean A1C decrease of 0.9%. The mean A1C was 7%. The mean FPG reduction was 50.4 mg/dL.1

bMinor=self measured plasma glucose <56 mg/dL and not requiring third-party assistance; major=requiring third-party assistance.

Adapted from Blonde et al, 2009.1

aLevemir® can be dosed once or twice daily.2



All patients received Levemir® injection once daily1,a

In the same study, mean FPG values decreased in the first 8 weeks, then remained generally flat, with a total drop of 57.6 mg/dL in the 70-90 mg/dL group and 50.4 mg/dL drop in the 80-110 mg/dL group.1
 

In TRANSITION™, a 26-week randomized clinical trial3:

Low rates of minor hypoglycemia in patients being treated with metformin + sitagliptin + Levemir®3,c

The TRANSITION™ clinical trial showed low rates of minor hypoglycemia in patients treated with metformin + sitagliptin + Levemir®

Results from TRANSITION, a 26-week, open-label, randomized, parallel-group study in patients with type 2 diabetes. Insulin-naïve patients concomitantly treated with metformin +/– a second OAD were randomized to receive either once-dailya Levemir® + sitagliptin + metformin (n=111; metformin continued while all other OADs discontinued) or sitagliptin + metformin +/– sulfonylurea (SU) (n=111; metformin and SU continued while all other OADs discontinued. SU was allowed to be discontinued at the discretion of the investigator.) The primary study end point was A1C after 26 weeks.3

cMinor = self-treatable and plasma glucose (PG) <56 mg/dL, with or without symptoms; major = unable to self-treat.

Adapted from Hollander et al, 2011.3


 

There were no major hypoglycemic events in either treatment group3

In the same study, mean FPG decreased by 66.3 mg/dL after 26 weeks in the metformin + sitagliptin + Levemir® arm and by 22.2 mg/dL in the metformin + sitagliptin ± SU arm.3

 

In DeVries et al; combination study4:

Low rates of hypoglycemia over 26 weeks in patients being treated with metformin + Victoza®d + Levemir®2,3,e-g

DeVries et al was a 26-week combination study of patients treated with metformin + Victoza® + Levemir®

dVictoza® is a GLP-1 receptor agonist.

eDuring the main treatment period.

fNonsevere=PG <56 mg/dL (patients able to self-treat).
Severe=any event requiring third-party assistance irrespective of PG levels.

gOne patient in the metformin + Victoza® arm was excluded due to the 25 hypoglycemic episodes that the patient was able to self-treat. This patient had a history of frequent hypoglycemia prior to the study.

This was a multinational, open-label study of 988 insulin-naïve adults with type 2 diabetes (aged 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-dailya Levemir® as add-on therapy or to continued, unchanged treatment with Victoza® 1.8 mg and metformin.4

Adapted from DeVries et al, 2012.4

 

In the same study, there were significant reductions in A1C and FPG over 26 weeks when Levemir® once dailyb was added to metformin + Victoza®.2,3

 

Levemir® With GLP-1 Receptor Agonist

This study also showed significant reductions in A1C and FPG over 26 weeks.4



In PREDICTIVE, an observational trial6:

Once-dailya efficacy and low rates of hypoglycemia were also shown in patients with type 2 diabetes in whom Levemir® was added to OADs or patients were converted at baseline from other basal insulin therapies +/– OADs or patients were converted at baseline from other basal insulin therapies +/– OADs6

Results from the German cohort of PREDICTIVE (n=10,276): a multicenter observational study evaluating the efficacy and safety of Levemir® in patients with diabetes over 14.5 weeks. Subgroup analysis of patients with type 2 diabetes further evaluated the efficacy and safety of Levemir® when adding to or switching from OAD therapy (n=1321); NPH insulin ± OAD therapy (n=251); or insulin glargine U-100 ± OAD therapy (n=260).6

Adapted from Meneghini et al, 2007.6




 

Related Safety Topics:

References
  1. 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;11(6):623-631.
  2. Levemir [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2015.
  3. Hollander P, Raslova K, Skjøth TV, Råstam J, Liukus JF. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial. Diabetes Obes Metab. 2011;13(3):268-275.
  4. DeVries JH, Bain SC, Rodbard HW, et al. 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.
  5. Meneghini LF, Rosenberg KH, Koenen C, Merilainen MJ, Lüddeke H-J. Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain in patients with type 2 diabetes who were insulin naïve or treated with NPH or insulin glargine: clinical practice experience from a German subgroup of the PREDICTIVE study. Diabetes Obes Metab. 2007;9(3):418-427.

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

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 the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
  • 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). Counsel patients regarding the potential risk for MTC with the use of Victoza® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Victoza®.

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 Levemir® Prescribing Information.

Victoza® (liraglutide) injection 1.2 mg or 1.8 mg Indication and Limitations of Use

Victoza® (liraglutide) injection 1.2 mg or 1.8 mg is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

  • Victoza® is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise.
  • Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with Victoza® postmarketing. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using Victoza®; consider other antidiabetic therapies for these patients.
  • Victoza® is not a substitute for insulin and should not be used in patients with type 1 diabetes mellitus or diabetic ketoacidosis.
  • Concurrent use with prandial insulin has not been studied.

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 the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
  • 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). Counsel patients regarding the potential risk for MTC with the use of Victoza® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Victoza®.

Contraindications

  • Victoza® is contraindicated in patients with a prior serious hypersensitivity reaction to Victoza® or to any of the product components.

Warnings and Precautions

  • Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.
  • Pancreatitis: Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with Victoza® postmarketing. Observe patients carefully for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back with or without vomiting). If pancreatitis is suspected, discontinue Victoza® promptly and if pancreatitis is confirmed, do not restart. Consider other antidiabetic therapies in patients with a history of pancreatitis.
  • Never Share a Victoza® Pen Between Patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.
  • Hypoglycemia: When Victoza® is used with an insulin secretagogue (eg, 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: Acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis, have been reported postmarketing, usually in association with nausea, vomiting, diarrhea, or dehydration. Use caution when initiating or escalating doses of Victoza®  in patients with renal impairment.
  • Hypersensitivity Reactions: Serious hypersensitivity reactions (eg, anaphylaxis and angioedema) have been reported postmarketing. If symptoms of hypersensitivity reactions occur, patients must stop taking Victoza®  and promptly seek medical advice.
  • Macrovascular Outcomes: There have been no studies establishing conclusive evidence of macrovascular risk reduction with Victoza® or any other antidiabetic drug.

Adverse Reactions

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

Drug Interactions

  • Victoza® causes a delay of gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with Victoza®.

Use in Specific Populations

  • Victoza® has not been studied in patients with type 2 diabetes 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.
  • Victoza® slows gastric emptying. Victoza® has not been studied in patients with preexisting gastroparesis.

Additional Important Safety Information

In 5 placebo-controlled clinical trials of at least 26 weeks’ duration, hypoglycemia requiring the assistance of another person for treatment occurred in 8 Victoza®-treated patients (7.5 events per 1000 patient-years). Of these 8 Victoza®-treated patients, 7 patients were concomitantly using a sulfonylurea.

In the pool of 5 placebo-controlled clinical trials, withdrawals due to gastrointestinal adverse reactions occurred in 4.3% of Victoza®-treated patients and 0.5% of placebo-treated patients. Withdrawal due to gastrointestinal adverse events mainly occurred during the first 2 to 3 months of the trials.

Please click here for Victoza® Prescribing Information.