Introduction
Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used primarily for the management of type 2 diabetes mellitus and chronic weight management. As a long-acting analog of human GLP-1, it enhances glucose-dependent insulin secretion while suppressing inappropriate glucagon secretion and delaying gastric emptying. Marketed under brand names including Victoza® (for diabetes) and Saxenda® (for weight management), liraglutide represents a significant advancement in metabolic disorder management.
Mechanism of Action
Liraglutide acts as an incretin mimetic by binding to and activating the GLP-1 receptor. This results in:
- Glucose-dependent stimulation of insulin secretion from pancreatic beta cells
- Suppression of inappropriately elevated glucagon secretion from pancreatic alpha cells
- Delay in gastric emptying, which reduces postprandial glucose excursions
- Promotion of satiety through central nervous system effects
- Potential preservation of beta-cell function
The drug's effects are glucose-dependent, meaning insulin secretion is enhanced when blood glucose levels are elevated, reducing the risk of hypoglycemia compared to other antidiabetic agents.
Indications
FDA-approved indications:- Type 2 diabetes mellitus (as an adjunct to diet and exercise)
- Chronic weight management in adults with:
- BMI ≥30 kg/m² (obesity) - BMI ≥27 kg/m² (overweight) with at least one weight-related comorbidity
- Reduction of cardiovascular risk in adults with type 2 diabetes and established cardiovascular disease
Dosage and Administration
For type 2 diabetes (Victoza®):- Initial dose: 0.6 mg subcutaneously once daily for 1 week
- Increase to 1.2 mg daily after first week
- May further increase to 1.8 mg daily if additional glycemic control needed
- Administer at any time of day, with or without meals
- Initial dose: 0.6 mg subcutaneously once daily
- Increase by 0.6 mg weekly to target dose of 3.0 mg daily
- Maximum dose: 3.0 mg daily
- Discontinue if 3.0 mg dose not tolerated after 4 weeks
- Renal impairment: No dosage adjustment needed for mild to moderate impairment; use with caution in severe impairment
- Hepatic impairment: No dosage adjustment needed
- Elderly: No dosage adjustment needed, but consider potential comorbidities
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Bioavailability is approximately 55% following subcutaneous administration. Maximum concentration reached in 8-12 hours. Distribution: Volume of distribution is approximately 13-15 L. Highly protein-bound (>98%). Metabolism: Undergoes endogenous degradation via ubiquitous proteolytic enzymes without specific organ involvement. Elimination: Half-life is approximately 13 hours, allowing for once-daily dosing. Primarily eliminated through metabolic pathways with negligible renal excretion.Contraindications
- Personal or family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Hypersensitivity to liraglutide or any product components
- Pregnancy (for weight management indication)
Warnings and Precautions
Boxed Warning: Risk of thyroid C-cell tumors. Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors in rats. Human relevance uncertain but contraindicated in patients with personal/family history of MTC or MEN 2. Additional warnings:- Pancreatitis: Discontinue promptly if pancreatitis suspected
- Hypoglycemia: Risk increased when used with insulin secretagogues or insulin
- Renal impairment: Monitor renal function in patients reporting severe gastrointestinal reactions
- Hypersensitivity reactions: Including anaphylaxis and angioedema
- Acute gallbladder disease: Has been reported in clinical trials
- Suicidal behavior and ideation: Monitor for emergence or worsening of depression
Drug Interactions
Significant interactions:- Insulin secretagogues (sulfonylureas): Increased risk of hypoglycemia (consider reducing secretagogue dose)
- Oral medications: Delayed gastric emptying may affect absorption of orally administered drugs
- Warfarin: Monitor INR more frequently when initiating or changing liraglutide dose
- Drugs that prolong QT interval: Theoretical risk of additive effects
Adverse Effects
Common adverse reactions (≥5%):- Nausea (20-40%)
- Diarrhea (9-21%)
- Constipation (10%)
- Vomiting (11-18%)
- Headache (9-14%)
- Decreased appetite (11%)
- Dyspepsia (7%)
- Pancreatitis
- Hypersensitivity reactions
- Renal impairment
- Gallbladder disease
- Increased heart rate (2-4 bpm)
- Thyroid C-cell tumors (in rodents)
Monitoring Parameters
- HbA1c every 3 months until stable, then every 6 months
- Fasting plasma glucose regularly
- Body weight (for both diabetes and weight management indications)
- Renal function (serum creatinine, BUN)
- Serum calcitonin (if indicated based on clinical findings)
- Signs/symptoms of pancreatitis
- Hypoglycemia symptoms, especially when used with other antidiabetic agents
- Depression or suicidal ideation (weight management indication)
Patient Education
- Proper injection technique and rotation of injection sites
- Importance of consistent timing of daily administration
- Recognition and management of hypoglycemia symptoms
- Report symptoms of pancreatitis (severe abdominal pain that may radiate to the back)
- Report symptoms of allergic reactions
- Inform all healthcare providers about liraglutide use
- Do not share pen devices with others
- Storage requirements: Refrigerate unused pens; may be stored at room temperature for in-use pens
- Gradual dose titration to minimize gastrointestinal side effects
- Importance of continued diet and exercise regimen
References
1. FDA Prescribing Information: Victoza® (liraglutide) injection. Revised 2023. 2. FDA Prescribing Information: Saxenda® (liraglutide) injection. Revised 2023. 3. Marso SP, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016;375(4):311-322. 4. Davies MJ, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes. JAMA. 2015;314(7):687-699. 5. 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. 6. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 7. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm. Endocr Pract. 2023;29(2):1-35.
Note: This monograph provides general information and should not replace professional medical advice. Always consult with qualified healthcare providers for personalized medical guidance.