Landmark CVOT

LEADER—a landmark cardiovascular outcomes trial for Victoza®1

Victoza® reduced the relative risk of major adverse cardiovascular events (MACE) by 13% (1.9% ARR).1,a

Components of the composite primary endpoint included1:

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CV death


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Nonfatal MI


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Nonfatal stroke

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aThe primary composite outcome occurred in fewer patients in the Victoza® group (608 of 4668 patients [13.0%]) than in the standard of care group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval, 0.78-0.97; (P=0.01).

In patients with type 2 diabetes and established CV disease

Victoza® is the only GLP-1 RA therapy approved to improve glycemic control and reduce the risk of major adverse cardiovascular events

Victoza® significantly reduced CV risk

Chart showing that Victoza significantly reduced cardiovascular (CV) risk

Absolute risk reduction

1.9%

Median time of exposure to treatment: 3.5 years.
Median daily dose of Victoza®: 1.78 mg.

The primary composite outcome occurred in fewer patients in the Victoza® group (608 of 4668 patients [13.0%]) than in the standard of care group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78-0.97; P=0.01).

Results for all 3 components of the primary composite endpoint supported the use of Victoza® vs standard of care alone

Chart showing that Victoza® significantly reduced the risk of composite primary endpoint, major adverse cardiovascular events (MACE)

In the LEADER trial

Victoza® provided a life-saving benefit1

Death from CV causes

Chart showing death from CV causes occurred in fewer patients in the Victoza group than in the standard care group

Absolute risk reduction

1.3%

Death from CV causes occurred in fewer patients in the Victoza® group (219 patients [4.7%]) than in the standard of care group (278 [6.0%]) (hazard ratio, 0.78; 95% CI; 0.66-0.93).

Absolute risk reduction

1.4%

Death from all causes occurred in fewer patients in the Victoza® group (381 patients [8.2%]) than in the standard of care group (447 patients [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74-0.97).

Death from CV causes was a prespecified secondary endpoint.

Hazard ratio, 0.78 (95% CI, 0.66-0.93).
Median time of exposure to treatment: 3.5 years.
Median daily dose of Victoza®: 1.78 mg.

In addition to CV risk reduction, Victoza® offers unsurpassed A1C reductions

Change the course of treatment with Victoza® for your patients with T2D and established CVD

The Victoza® patient*

See what patient types might benefit from a GLP-1 RA that reduces A1C and CV risk

*Not an actual patient.

Prescribing and dosing

Learn how to start and titrate patients on Victoza®

LEADER study design2

A phase 3B, multicenter, international, randomized, double-blind, placebo-controlled study to assess the cardiovascular safety of Victoza®. Patients with type 2 diabetes at high risk for cardiovascular events (N=9340) were randomized to receive once-daily Victoza® (0.6 mg – 1.8 mg QD with all patients being titrated to 1.8 mg QD) or placebo. The primary endpoint was the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial was prospectively designed and powered to assess whether Victoza® was noninferior or superior to placebo when measuring effect on CV events. Patients received trial products in addition to standard of care treatments such as oral antidiabetic treatments, insulin, and antihypertensive, antiplatelet, and lipid-lowering therapies.    


CKD= chronic kidney disease; CV=cardiovascular; CVOT=cardiovascular outcomes trial; MI=myocardial infarction; RRR=relative risk reduction.    


References:

  1. Marso SP, Daniels GH, Brown-Frandsen K, et al; the LEADER Steering Committee on behalf of the LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-322.
  2. Marso SP, Poulter NR, Nissen SE, et al. Design of the liraglutide effect and action in diabetes: evaluation or cardiovascular outcomes results (LEADER) trial. Am Heart J. 2013;166(5):823-830.    

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®.

Indications 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, and to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established CV disease.

  • 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 personal or family history of MTC or in patients with MEN 2, and in patients with a prior serious hypersensitivity reaction to Victoza® or to any of the product components. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with Victoza®.

Warnings and Precautions

  • Risk of Thyroid C-cell Tumors: Patients should be referred to an endocrinologist for further evaluation if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging.
  • 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. Victoza® has been studied in a limited number of patients with a history of pancreatitis. It is unknown if patients with a history of pancreatitis are at a higher risk for development of pancreatitis on Victoza®.
  • 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 post-marketing. If symptoms of hypersensitivity reactions occur, patients must stop taking Victoza®; treat promptly per standard of care, and monitor until signs and symptoms resolve.  Do not use in patients with a previous hypersensitivity reaction to Victoza®. Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists.  Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-receptor agonist because it is unknown whether such patients will be predisposed to these reactions with Victoza®.
  • Acute Gallbladder Disease: In the LEADER trial, 3.1% of Victoza® vs. 1.9% of placebo-treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis. The majority of events required hospitalization or cholecystectomy. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow up are indicated.

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, vomiting, decreased appetite, dyspepsia, and constipation. 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.
  • Victoza® slows gastric emptying. Victoza® has not been studied in patients with pre-existing gastroparesis.
  • Victoza® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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.

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