SEMAGLUTIDE

Peptide Data Sheet for Pharmacists and Compounding Professionals

BASIC INFORMATION

Name: Semaglutide
Class: Glucagon-like peptide-1 (GLP-1) receptor agonist
Structure: 31-amino acid peptide analog of human GLP-1
Molecular Weight: 4113.58 g/mol
Chemical Modifications:

  • C-18 fatty diacid chain attached to lysine at position 26
  • Amino acid substitution at position 8 (alanine to alpha-aminoisobutyric acid)

Available Forms:

  • FDA-approved injectable solutions (Ozempic®, Wegovy®)
  • FDA-approved oral tablets (Rybelsus®)
  • Compounded formulations (subject to regulatory requirements)

REGULATORY STATUS

FDA Status

  • Ozempic®: Approved for type 2 diabetes management
  • Wegovy®: Approved for chronic weight management
  • Rybelsus®: Approved for type 2 diabetes management (oral formulation)

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

Semaglutide 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
Mechanism of Action

PHARMACOKINETICS

| Parameter | Value | Notes | |———–|——-|——-| | Absorption | Subcutaneous: 89% bioavailability<br>Oral: ~1% bioavailability | Oral absorption enhanced by SNAC carrier | | Distribution | Volume of distribution: ~12.5 L | 99% plasma protein bound | | Metabolism | Proteolytic cleavage of peptide backbone and beta-oxidation | Resistant to DPP-4 degradation | | Elimination | Half-life: ~1 week | Primarily excreted in urine and feces |

CLINICAL APPLICATIONS

FDA-Approved Indications

  1. Type 2 Diabetes Management
    • Improves glycemic control
    • Reduces cardiovascular risk in patients with established CVD
    • Typical HbA1c reduction: 1.0-1.8%
  2. Chronic Weight Management
    • For adults with BMI ≥30 kg/m², or ≥27 kg/m² with weight-related comorbidity
    • Average weight loss: 15-18% of body weight over 68 weeks
    • Maintenance of weight loss with continued therapy

Off-Label/Investigational Uses

  • Non-alcoholic steatohepatitis (NASH)
  • Polycystic ovary syndrome (PCOS)
  • Cardiovascular risk reduction in non-diabetic patients
  • Neurodegenerative disorders (early research)

DOSING GUIDELINES

Type 2 Diabetes (Ozempic®)

| Week | Dose | Administration | |——|——|—————-| | 1-4 | 0.25 mg | Once weekly, subcutaneous | | 5-8 | 0.5 mg | Once weekly, subcutaneous | | 9+ | 1.0 mg | Once weekly, subcutaneous | | Maintenance | Up to 2.0 mg | Once weekly, subcutaneous |

Weight Management (Wegovy®)

| Week | Dose | Administration | |——|——|—————-| | 1-4 | 0.25 mg | Once weekly, subcutaneous | | 5-8 | 0.5 mg | Once weekly, subcutaneous | | 9-12 | 1.0 mg | Once weekly, subcutaneous | | 13-16 | 1.7 mg | Once weekly, subcutaneous | | 17+ | 2.4 mg | Once weekly, subcutaneous |

Oral Semaglutide (Rybelsus®)

| Week | Dose | Administration | |——|——|—————-| | 1-4 | 3 mg | Once daily, oral | | 5-8 | 7 mg | Once daily, oral | | 9+ | 14 mg | Once daily, oral |

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)
  • May be stored at room temperature (up to 30°C/86°F) for up to 56 days

Oral Administration (Rybelsus®)

  • Take on empty stomach upon waking
  • Take with no more than 4 ounces of plain water
  • Wait at least 30 minutes before eating, drinking, or taking other oral medications
  • Swallow tablet whole (do not crush, cut, or chew)

SAFETY PROFILE

Contraindications

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

Warnings and Precautions

  • Boxed Warning: Risk of thyroid C-cell tumors
  • Pancreatitis
  • Diabetic retinopathy complications
  • Acute kidney injury
  • Hypoglycemia (when used with insulin or insulin secretagogues)
  • Acute gallbladder disease
  • Hypersensitivity reactions

Common Adverse Effects

| System | Adverse Effects | Approximate Incidence | |——–|—————-|————————| | Gastrointestinal | Nausea | 15-44% | | | Vomiting | 6-25% | | | Diarrhea | 8-17% | | | Abdominal pain | 10-18% | | | Constipation | 5-10% | | General | Fatigue | 5-11% | | | Injection site reactions | 1-3% | | Metabolic | Decreased appetite | 8-10% |

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, moderate, or severe hepatic impairment
  • Limited clinical experience in severe 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: Not recommended for use in pregnancy
  • Lactation: Unknown if excreted in human milk; use caution

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
  • Once-weekly formulations stable at room temperature for up to 56 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
    • Visual changes

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: Weekly dosing improves compliance compared to daily medications
  • Cost: Patient assistance programs, insurance prior authorizations

REFERENCES

  1. FDA. Ozempic (semaglutide) Prescribing Information.
  2. FDA. Wegovy (semaglutide) Prescribing Information.
  3. FDA. Rybelsus (semaglutide) Prescribing Information.
  4. Davies M, 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.
  5. Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375(19):1834-1844.