What to do for an adult patient with type 2 diabetes experiencing welts at the Glucagon-like peptide-1 (GLP1) injection site?

Management of Welts at GLP-1 Injection Sites

Welts at GLP-1 injection sites represent a local injection site reaction that requires immediate assessment of injection technique, systematic site rotation, and evaluation for lipohypertrophy or subcutaneous nodules—if these measures fail to resolve the issue within 2-4 weeks, consider switching to an alternative GLP-1 receptor agonist formulation.

Immediate Assessment and Intervention

Evaluate Current Injection Technique

• Use 4-mm pen needles inserted at 90 degrees for all adults regardless of BMI, as this is the recommended standard for GLP-1 receptor agonists following the same guidelines as insulin administration 1.
• Verify the patient is injecting into subcutaneous tissue, not intramuscularly or intradermally, as improper depth can cause local reactions 1.
• Confirm injection sites include the abdomen (2 fingerbreadths from umbilicus), upper third anterior lateral thighs, posterior lateral upper buttocks/flanks, or middle third posterior upper arm 1.

Assess for Lipohypertrophy and Subcutaneous Nodules

• Palpate and visually examine all injection sites for lipohypertrophy (soft, smooth raised areas several centimeters in breadth) or subcutaneous nodules, which have been specifically reported with once-weekly exenatide and semaglutide 1.
• Mark the borders of any identified lipohypertrophy or nodules with skin-safe markers and instruct the patient to completely avoid these areas until they resolve 1.
• Document findings with body maps, size descriptors, or photography with patient consent to track evolution over time 1.

Implement Strict Site Rotation Protocol

Systematic Rotation Strategy

• Instruct the patient to rotate injection sites systematically both between anatomical sites (abdomen, thigh, buttock, arm) and within each site, maintaining at least 1-2 cm spacing between injection points 1.
• Provide injection site map handouts or recommend injection rotation apps to encourage adherence to regular rotation 1.
• The risk of lipohypertrophy is considerably less with GLP-1 receptor agonists compared to insulin, but proper rotation remains essential 1.

Avoid Common Pitfalls

• Ensure the patient avoids injecting cold medication directly from refrigeration, as this can contribute to local reactions 1.
• Confirm the patient is not reusing needles, as needle reuse increases the risk of lipohypertrophy and injection site complications 1.
• Verify injections avoid bony prominences by 1-2 fingerbreadths and stay clear of scars or areas of previous lipohypertrophy 1.

Medication-Specific Considerations

Adjust Administration Timing

• For daily or twice-daily GLP-1 formulations, ensure injections are administered premeal as recommended 1, 2.
• Once-weekly formulations can be taken at any time regardless of meals, which may allow flexibility in site selection 1, 2.

Consider Formulation Switch if Persistent

• If welts persist despite proper technique and rotation after 2-4 weeks, consider switching to an alternative GLP-1 receptor agonist, as subcutaneous nodules have been specifically reported with certain formulations (once-weekly exenatide and semaglutide) 1.
• Longer-acting GLP-1 receptor agonists generally have fewer gastrointestinal side effects and may have different local tolerability profiles 3, 4.

Monitor for Resolution and Complications

Follow-Up Timeline

• Reassess injection sites at 2-week intervals initially to monitor for improvement or worsening 1.
• All patients using injectable diabetes medications must have their sites checked at every regular visit, or at least annually 1.

Red Flags Requiring Further Evaluation

• If welts are accompanied by signs of infection (warmth, erythema spreading beyond injection site, purulent drainage), this requires immediate medical attention beyond simple technique correction 1.
• Persistent nodules that do not resolve with site avoidance may represent amyloidosis (accumulation of amyloid deposits), a rare form of lipodystrophy requiring specialist consultation 1.
• Erratic glucose control or unexplained glycemic variability may indicate injection into areas of lipodystrophy affecting drug absorption 1.

Patient Education Priorities

Key Teaching Points

• Teach patients to self-inspect sites and distinguish healthy from unhealthy tissue, as early detection prevents progression 1.
• Emphasize that injection into sites of lipodystrophy causes erratic drug absorption and should be completely avoided 1.
• Gradual dose titration minimizes gastrointestinal side effects but does not prevent injection site reactions—these require technique modification 1, 2, 3.