LIRAGLUTIDE

Peptide Data Sheet for Pharmacists and Compounding Professionals

BASIC INFORMATION

Name: Liraglutide
Class: Glucagon-like peptide-1 (GLP-1) receptor agonist
Structure: 31-amino acid peptide analog of human GLP-1
Molecular Weight: 3751.2 g/mol
Chemical Modifications:

  • C16 fatty acid (palmitic acid) chain attached to lysine at position 26 via a glutamic acid spacer
  • Substitution of lysine for arginine at position 34

Available Forms:

  • FDA-approved injectable solutions (Victoza®, Saxenda®)
  • Compounded formulations (subject to regulatory requirements)

REGULATORY STATUS

FDA Status

  • Victoza®: Approved for type 2 diabetes management (2010)
  • Saxenda®: Approved for chronic weight management (2014)

Compounding Considerations

  • Compounding must comply with USP <797> standards
  • Not eligible for compounding when FDA-approved versions are commercially available unless clinical need for modification is documented
  • Requires sterile compounding techniques

MECHANISM OF ACTION

Liraglutide activates the GLP-1 receptor to:

  • Increase glucose-dependent insulin secretion
  • Decrease inappropriate glucagon secretion
  • Slow gastric emptying
  • Reduce food intake through increased satiety and reduced hunger
  • Improve beta-cell function

The C16 fatty acid chain enables binding to albumin, which:

  • Protects against metabolic degradation
  • Reduces renal clearance
  • Extends half-life to approximately 13 hours
Mechanism of Action

PHARMACOKINETICS

| Parameter | Value | Notes | |———–|——-|——-| | Absorption | Subcutaneous: 55% bioavailability | Slow absorption from injection site | | Distribution | Volume of distribution: 11-17 L | >98% plasma protein bound | | Metabolism | Proteolytic degradation | Resistant to DPP-4 degradation | | Elimination | Half-life: ~13 hours | No intact liraglutide excreted in urine or feces |

CLINICAL APPLICATIONS

FDA-Approved Indications

  1. Type 2 Diabetes Management (Victoza®)
    • Improves glycemic control as adjunct to diet and exercise
    • Reduces risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease
    • Typical HbA1c reduction: 0.8-1.5%
  2. Chronic Weight Management (Saxenda®)
    • For adults with BMI ≥30 kg/m², or ≥27 kg/m² with weight-related comorbidity
    • Average weight loss: 5-10% of body weight
    • Maintenance of weight loss with continued therapy

Off-Label/Investigational Uses

  • Non-alcoholic steatohepatitis (NASH)
  • Polycystic ovary syndrome (PCOS)
  • Neurodegenerative disorders (early research)

DOSING GUIDELINES

Type 2 Diabetes (Victoza®)

| Week | Dose | Administration | |——|——|—————-| | 1 | 0.6 mg | Once daily, subcutaneous | | 2+ | 1.2 mg | Once daily, subcutaneous | | Maintenance (if needed) | 1.8 mg | Once daily, subcutaneous |

Weight Management (Saxenda®)

| Week | Dose | Administration | |——|——|—————-| | 1 | 0.6 mg | Once daily, subcutaneous | | 2 | 1.2 mg | Once daily, subcutaneous | | 3 | 1.8 mg | Once daily, subcutaneous | | 4 | 2.4 mg | Once daily, subcutaneous | | 5+ | 3.0 mg | Once daily, subcutaneous |

Dose Adjustments:

  • Dose escalation may be delayed based on tolerability
  • If 3.0 mg dose is not tolerated, may reduce to 2.4 mg
  • Evaluate weight loss after 16 weeks on 3.0 mg; discontinue if <4% weight loss

ADMINISTRATION

Subcutaneous Injection

  • Administer in abdomen, thigh, or upper arm
  • Rotate injection sites
  • May be administered without regard to meals
  • Store refrigerated (2-8°C/36-46°F)
  • After first use, may be stored at room temperature (below 30°C/86°F) for up to 30 days

SAFETY PROFILE

Contraindications

  • Personal or family history of medullary thyroid carcinoma
  • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
  • Hypersensitivity to liraglutide or any excipients
  • Pregnancy (Saxenda®)

Warnings and Precautions

  • Boxed Warning: Risk of thyroid C-cell tumors
  • Pancreatitis
  • Acute gallbladder disease
  • Hypoglycemia (when used with insulin or insulin secretagogues)
  • Acute kidney injury
  • Hypersensitivity reactions
  • Suicidal behavior and ideation (Saxenda®)

Common Adverse Effects

| System | Adverse Effects | Approximate Incidence | |——–|—————-|————————| | Gastrointestinal | Nausea | 20-40% | | | Vomiting | 5-15% | | | Diarrhea | 10-20% | | | Constipation | 10-20% | | | Dyspepsia | 5-10% | | General | Headache | 10-15% | | | Injection site reactions | 2-5% | | Metabolic | Decreased appetite | 10-20% |

Drug Interactions

  • Delayed absorption of oral medications due to slowed gastric emptying
  • Increased risk of hypoglycemia when used with insulin or insulin secretagogues
  • Potential additive effects with other medications that cause hypoglycemia

SPECIAL POPULATIONS

Renal Impairment

  • No dose adjustment required for mild, moderate, or severe renal impairment
  • Limited experience in end-stage renal disease
  • Monitor renal function when initiating or escalating doses

Hepatic Impairment

  • No dose adjustment required for mild or moderate hepatic impairment
  • Limited clinical experience in severe hepatic impairment
  • Use with caution in patients with hepatic impairment

Geriatric Patients

  • No dose adjustment required based on age
  • Greater sensitivity in some older individuals
  • Start at lower doses and titrate more slowly if needed

Pregnancy and Lactation

  • Pregnancy:
    • Victoza®: Use only if potential benefit justifies potential risk to fetus
    • Saxenda®: Contraindicated during pregnancy
  • Lactation: Unknown if excreted in human milk; use caution

Pediatric Patients

  • Victoza®: Approved for patients 10 years and older with type 2 diabetes
  • Saxenda®: Approved for patients 12 years and older with body weight >60 kg and obesity

PHARMACIST GUIDANCE

Compounding Considerations

  • Requires aseptic technique and sterile compounding environment
  • Stability affected by temperature, pH, and mechanical agitation
  • Incompatible with strongly acidic or basic solutions
  • Adhere to USP <797> standards for sterile compounding

Storage and Handling

  • Store in refrigerator (2-8°C/36-46°F)
  • Protect from light
  • Do not freeze
  • Discard if frozen
  • After first use, may be stored at room temperature (below 30°C/86°F) for up to 30 days

Patient Counseling Points

  1. Administration Technique
    • Proper subcutaneous injection technique
    • Importance of injection site rotation
    • Proper disposal of needles and syringes
  2. Gastrointestinal Side Effects
    • Typically transient and decrease over time
    • Small, frequent meals may help
    • Adequate hydration important
    • Contact healthcare provider if severe or persistent
  3. Hypoglycemia Risk
    • Signs and symptoms of hypoglycemia
    • Proper management of hypoglycemia
    • Importance of blood glucose monitoring
  4. Monitoring Parameters
    • Regular monitoring of blood glucose
    • Regular monitoring of weight
    • Regular monitoring of renal function
    • Regular monitoring of pancreatic enzymes if symptoms of pancreatitis
  5. When to Seek Medical Attention
    • Severe abdominal pain (potential pancreatitis)
    • Persistent vomiting or inability to maintain hydration
    • Signs of allergic reaction
    • Suicidal thoughts or behaviors

MAXIMIZING THERAPEUTIC OUTCOMES

Optimizing Efficacy

  • Gradual dose titration minimizes GI side effects and improves tolerability
  • Combination with lifestyle modifications enhances weight loss and glycemic control
  • Patient education improves adherence and outcomes
  • Regular follow-up and monitoring optimizes dose and manages side effects

Managing Common Challenges

  • GI Side Effects: Slow titration, small frequent meals, adequate hydration
  • Injection Site Reactions: Proper technique, site rotation, room temperature injection
  • Adherence: Daily dosing requires consistent routine
  • Cost: Patient assistance programs, insurance prior authorizations

Comparative Efficacy

| Outcome | Liraglutide | Semaglutide | Notes | |———|————-|————-|——-| | HbA1c Reduction | 0.8-1.5% | 1.0-1.8% | Semaglutide generally more potent | | Weight Loss | 5-10% | 15-18% | Semaglutide generally more effective | | Dosing | Daily | Weekly | Weekly dosing may improve adherence | | CV Benefit | Established | Established | Both reduce major adverse CV events |

REFERENCES

  1. FDA. Victoza (liraglutide) Prescribing Information.
  2. FDA. Saxenda (liraglutide) Prescribing Information.
  3. Davies MJ, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA. 2015;314(7):687-699.
  4. Marso SP, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016;375(4):311-322.
  5. Mehta A, et al. Liraglutide for weight management: a critical review of the evidence. Obes Sci Pract. 2017;3(1):3-14.