Why are a patient's hands and feet turning orange while taking semaglutide (GLP-1 receptor agonist)?

Orange Discoloration of Hands and Feet in Patients Taking Semaglutide

Semaglutide does not directly cause orange discoloration of hands and feet, as this is not a documented side effect of GLP-1 receptor agonists in medical literature. The discoloration is likely related to other factors that should be investigated.

Possible Explanations for Orange Discoloration

• Dermatological reactions: While not specifically causing orange discoloration, semaglutide has been associated with dermatological hypersensitivity reactions that may manifest as skin eruptions 1

• Carotenemia: Rapid weight loss from semaglutide may lead to increased concentration of fat-soluble vitamins and carotenoids in the skin, potentially causing yellowish-orange discoloration, particularly in areas with thicker skin like palms and soles 2

• Skin changes related to weight loss: The significant weight loss associated with semaglutide (6.1-17.4% in non-diabetic patients) may cause changes in skin appearance and coloration 3

Known Side Effects of Semaglutide

• Gastrointestinal effects: The most common side effects of semaglutide are nausea, vomiting, diarrhea, dyspepsia, and gastrointestinal reflux 3

• Delayed gastric emptying: Semaglutide can significantly delay gastric emptying, which contributes to its weight loss effects but also to gastrointestinal side effects 3

• Skin-related reactions: Some patients experience dermal hypersensitivity reactions and skin tenderness (allodynia) with semaglutide use 1, 4

• Facial aging ("Ozempic face"): Rapid weight loss from semaglutide can lead to facial aging due to decreased facial fat and potentially direct effects on adipose-derived stem cells and fibroblasts 2

Clinical Approach for Orange Discoloration

1. Rule out other causes:

   • Evaluate dietary habits (high intake of carotenoid-rich foods like carrots, sweet potatoes)
   • Check medication list for other drugs that could cause skin discoloration
   • Assess liver and kidney function (as impaired function can affect drug metabolism) 3

2. Examine pattern and progression:

   • Document when discoloration began relative to starting semaglutide
   • Note if discoloration is limited to hands and feet or present elsewhere
   • Determine if discoloration is associated with other symptoms 1

3. Consider dermatology consultation:

   • If discoloration persists or is accompanied by other skin changes
   • To rule out other dermatological conditions 1, 4

Management Considerations

• Continue monitoring if discoloration is mild and not bothersome to the patient 4

• Dose adjustment may be considered if discoloration is concerning or accompanied by other side effects 3

• Discontinuation of semaglutide should be considered if discoloration is severe or associated with hypersensitivity reactions 1, 4

• Reassurance that many side effects of semaglutide, including skin-related issues, may resolve with continued use or after discontinuation 4

Important Caveats

• Semaglutide has significant cardiovascular and renal benefits that should be weighed against side effects when considering medication changes 3

• The orange discoloration is not listed as a common or recognized side effect in clinical trials or FDA labeling 5, 6

• If the patient has diabetes and chronic kidney disease, semaglutide remains a recommended agent with proven benefits 3

• Consider that the discoloration may be unrelated to semaglutide and could represent a coincidental finding requiring separate evaluation 1, 2