Victoza - Drug Monograph

Introduction

Victoza (liraglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist manufactured by Novo Nordisk. It is an injectable medication approved for the management of type 2 diabetes mellitus and, at a higher dose, for chronic weight management. As a GLP-1 analog, Victoza represents a significant advancement in diabetes care by addressing multiple pathophysiological defects while offering cardiovascular benefits.

Mechanism of Action

Liraglutide acts as a GLP-1 receptor agonist, mimicking the effects of endogenous GLP-1. Its primary mechanisms include:

• Glucose-dependent stimulation of insulin secretion from pancreatic β-cells
• Suppression of glucagon secretion from pancreatic α-cells
• Slowing gastric emptying, which reduces postprandial glucose excursions
• Promoting satiety and reducing food intake through central nervous system effects
• At higher doses (3.0 mg), it produces greater weight loss effects through enhanced satiety signaling

Unlike native GLP-1, liraglutide has a prolonged duration of action due to its structural modification (acylation with a fatty acid side chain) that promotes binding to albumin and resistance to degradation by dipeptidyl peptidase-4 (DPP-4).

Indications

• Type 2 diabetes mellitus: As an adjunct to diet and exercise to improve glycemic control
• Chronic weight management: As an adjunct to a reduced-calorie diet and increased physical activity for adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity

Dosage and Administration

• Initial dose: 0.6 mg subcutaneously once daily for at least one week
• Maintenance dose: Increase to 1.2 mg daily; may further increase to 1.8 mg daily if needed
• Maximum dose: 1.8 mg daily

• Initiation: 0.6 mg daily for one week, with weekly increments of 0.6 mg
• Maintenance dose: 3.0 mg daily
• Maximum dose: 3.0 mg daily

• Administer subcutaneously in abdomen, thigh, or upper arm
• Can be given without regard to meals
• Time of administration should be consistent each day

• Renal impairment: No dose adjustment needed for mild to moderate impairment; use caution in severe impairment
• Hepatic impairment: No dose adjustment recommended
• Elderly: No dose adjustment necessary
• Pediatrics: Not recommended for patients under 18 years

Pharmacokinetics

• Peak plasma concentrations reached in 8-12 hours
• Bioavailability: Approximately 55%

• Volume of distribution: ~13 L
• Highly protein-bound (>98%) to albumin

• Undergoes endogenous metabolism via proteolytic cleavage
• No specific cytochrome P450 enzyme involvement

• Half-life: ~13 hours
• Clearance: ~1.2 L/h
• Primarily eliminated through urine and feces as metabolites

Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC)
• Patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• History of hypersensitivity to liraglutide or any product components
• Pregnancy (based on animal data showing fetal harm)

Warnings and Precautions

• Thyroid C-cell tumors: Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors in rats. Relevance to humans unknown but contraindicated in patients with personal/family history of MTC.

• Pancreatitis: Discontinue promptly if pancreatitis is suspected
• Hypoglycemia: Increased risk when used with insulin or insulin secretagogues
• Renal impairment: Monitor renal function; cases of acute renal failure reported
• Hypersensitivity reactions: Anaphylaxis and angioedema reported
• Acute gallbladder disease: Increased risk observed
• Suicidal behavior and ideation: Monitor for emergence or worsening of depression

Drug Interactions

• Insulin and insulin secretagogues: Increased risk of hypoglycemia (dose reduction may be needed)
• Oral medications: May delay gastric emptying and affect absorption of orally administered drugs
• Warfarin: Monitor INR regularly (potential interaction)
• Drugs that prolong QT interval: Theoretical risk of additive effects

Adverse Effects

• Nausea (40%)
• Diarrhea (21%)
• Vomiting (16%)
• Constipation (14%)
• Headache (14%)
• Decreased appetite (11%)
• Dyspepsia (10%)
• Fatigue (9%)
• Dizziness (8%)
• Abdominal pain (8%)

• Pancreatitis
• Hypersensitivity reactions
• Acute kidney injury
• Gallbladder disease
• Increased heart rate
• Thyroid C-cell tumors (in rodents)

Monitoring Parameters

• HbA1c: Every 3 months until stable, then every 6 months
• Fasting glucose: Regularly
• Weight: At each visit
• Renal function: Baseline and periodically
• Lipase/amylase: If symptoms of pancreatitis occur
• Thyroid nodules: Baseline and periodically (neck examination)
• Heart rate: Monitor for tachycardia
• Depression screening: Especially in weight management patients

Patient Education

• Proper injection technique and rotation of injection sites
• Potential for gastrointestinal side effects (usually transient)
• Importance of not sharing pens between patients
• Recognition of hypoglycemia symptoms and management
• Signs of pancreatitis (severe abdominal pain with/without vomiting)
• Storage requirements: Refrigerate before first use; after first use, may store at room temperature
• Never use after expiration date
• Report any thyroid symptoms (lump in neck, hoarseness, difficulty swallowing)
• Inform all healthcare providers about Victoza use
• Continue adherence to diet and exercise recommendations

References

1. FDA Prescribing Information: Victoza (liraglutide) injection. Revised 2023. 2. Marso SP, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016;375(4):311-322. 3. Davies MJ, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes. JAMA. 2015;314(7):687-699. 4. Pi-Sunyer X, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015;373(1):11-22. 5. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 6. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology. Endocr Pract. 2020;26(1):1-46.