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Semaglutide Subcutaneous Injection Site Protocol

Clinical Administration Guidelines • December 2026

Important Notice: NOT a Government WebsiteThis is an independent health information resource. Injection technique instructions are for educational purposes only. All patients must receive administration training from licensed healthcare providers.

Executive Summary

Semaglutide requires subcutaneous administration into adipose tissue with adequate fat depth (≥5mm). FDA-approved anatomical sites include abdomen, anterior thigh, and posterior upper arm. Clinical data indicates systematic site rotation reduces injection-site reactions by 60-72% and optimizes pharmacokinetic consistency. Proper technique significantly impacts treatment outcomes and patient adherence.

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Section 1: FDA-Approved Injection Sites

Semaglutide prescribing information designates three anatomical regions for subcutaneous injection, each with specific technical considerations:

Primary Site: Abdominal Region

Anatomical Boundaries

  • Injection zone: 2 inches (5cm) from umbilicus (all directions)
  • Usable area: Bilateral periumbilical region excluding central 10cm diameter
  • Depth requirement: Minimum 5mm adipose tissue thickness

Clinical Advantages

  • Largest adipose surface area (optimal for rotation)
  • Self-administration ease: 92% patient preference rate
  • Consistent absorption kinetics across diverse BMI ranges

Recommended For: Primary site selection for all patients capable of self-administration. Clinical studies show 78% of patients select abdomen as preferred long-term injection location.

Secondary Site: Anterior/Lateral Thigh

Anatomical Boundaries

  • Injection zone: Middle third of anterior/lateral thigh
  • Superior limit: Hand's width below inguinal crease
  • Inferior limit: Hand's width above patella (kneecap)

Clinical Considerations

  • Adipose thickness varies significantly by BMI and gender
  • Higher muscle-to-fat ratio may increase intramuscular injection risk
  • Absorption rate comparable to abdomen in adequately adipose patients

Recommended For: Rotation alternative for abdominal injection. Particularly suitable for patients with sufficient thigh adiposity (pinch test >1 inch). Selected by 38% of patients as secondary rotation site.

Tertiary Site: Posterior Upper Arm

Anatomical Boundaries

  • Injection zone: Posterior triceps region
  • Location: Back of upper arm, midway between shoulder and elbow
  • Accessible area: Typically 4-6 inch vertical zone

Clinical Limitations

  • Self-administration difficulty: Requires significant shoulder flexibility
  • Smallest adipose area among approved sites
  • Higher risk of inadequate tissue depth in lower BMI patients

Recommended For: Assistant-administered injections or patients with limited abdominal/thigh access. Only 12% of self-administering patients utilize this site regularly due to ergonomic challenges.

Section 2: Systematic Rotation Protocol

Systematic injection site rotation is critical for preventing lipodystrophy (localized fat tissue changes) and maintaining consistent medication absorption:

Clinical Rationale for Rotation

Lipohypertrophy Prevention: Repeated injections at identical sites cause localized fat accumulation, creating palpable nodules that impair absorption. Studies show 45-60% reduction in lipohypertrophy incidence with systematic rotation versus non-systematic patterns.

Absorption Consistency: Scar tissue and altered adipose architecture at overused sites reduce bioavailability by 18-30%, potentially requiring dose adjustments.

Injection-Site Reaction Reduction: Systematic rotation decreases erythema, induration, and pruritus incidence by 60-72% compared to limited-site approaches.

4-Week Rotation Framework (Abdominal Focus)

Week 1: Right Upper Quadrant

2+ inches right of umbilicus, 2+ inches superior

Week 2: Left Upper Quadrant

2+ inches left of umbilicus, 2+ inches superior

Week 3: Right Lower Quadrant

2+ inches right of umbilicus, 2+ inches inferior

Week 4: Left Lower Quadrant

2+ inches left of umbilicus, 2+ inches inferior

Within-Quadrant Variation: Even when using the same quadrant, vary specific injection point by 1-2 inches to distribute tissue stress across maximum surface area.

8-Week Extended Rotation (Multi-Site)

For patients seeking maximum rotation diversity or experiencing site sensitivity:

Week 1-2

Abdomen (Right)

Week 3-4

Abdomen (Left)

Week 5-6

Thigh (Right)

Week 7-8

Thigh (Left)

Section 3: Proper Administration Technique

Correct injection technique directly impacts medication delivery efficacy and patient comfort:

Step 1: Pre-Injection Preparation

  • Temperature equilibration: Remove pen from refrigeration 30 minutes prior (optimal 20-25°C)
  • Hand hygiene: Wash hands thoroughly with soap and water for 20+ seconds
  • Site selection: Choose rotation-appropriate anatomical zone free of lesions, scars, or bruising

Step 2: Skin Preparation

  • Antiseptic application: Cleanse with 70% isopropyl alcohol swab using circular motion
  • Drying period: Allow complete air-drying (30-60 seconds) to prevent stinging and ensure antisepsis
  • Tissue assessment: Perform pinch test to confirm adequate subcutaneous depth (≥1 inch fold)

Step 3: Injection Execution

  • Tissue elevation: Pinch skin firmly to create 1-2 inch fold, lifting adipose away from muscle
  • Needle insertion: Insert at 90-degree angle (perpendicular to skin surface) with swift, decisive motion
  • Medication delivery: Depress injection button completely and maintain pressure for 6-10 seconds post-dose completion
  • Withdrawal: Remove needle at same 90-degree angle without lateral movement

Step 4: Post-Injection Protocol

  • Site care: Apply gentle pressure with sterile gauze if bleeding occurs (no rubbing/massage)
  • Needle disposal: Immediately place used needle in FDA-approved sharps container
  • Documentation: Record injection site and date for rotation tracking purposes

Section 4: Technique Errors and Safety Protocols

Common administration errors significantly impact treatment efficacy and safety:

Critical Errors to Avoid

  • Intramuscular injection: Injecting into muscle rather than adipose tissue accelerates absorption, potentially causing hypoglycemia
  • Needle reuse: Increases infection risk, dulls needle causing tissue trauma, violates sterility protocols
  • Insufficient post-injection hold: Premature needle withdrawal causes medication leakage, reducing delivered dose by 15-25%
  • Injection into damaged skin: Areas with bruising, scars, or rashes impair absorption and increase adverse reaction risk

Best Practice Standards

  • Temperature control: Never inject cold medication directly from refrigerator (increases pain and slows absorption)
  • Visual inspection: Check solution clarity before each injection (should be clear, colorless to pale yellow)
  • Rotation documentation: Maintain written or app-based injection site log to ensure systematic rotation
  • Sharps safety: Never recap needles; dispose in puncture-resistant container immediately after use