Can Metformin Cause Rash?
Yes, metformin can cause skin rash, including rash as a documented adverse reaction, though it is relatively uncommon compared to its gastrointestinal side effects. The FDA drug label for metformin specifically lists rash as one of the adverse reactions reported in clinical trials 1.
Evidence for Metformin-Associated Skin Reactions
FDA-Documented Adverse Reactions
According to the FDA drug label for metformin, rash is reported as an adverse reaction that occurred in ≥1% to ≤5% of metformin-treated patients and was more commonly reported with metformin than placebo 1. This places rash among the less common but documented side effects of the medication.
Case Reports
Several case reports in the medical literature document specific types of skin reactions associated with metformin:
A 29-year-old woman developed a facial skin rash during treatment with metformin. The rash improved upon discontinuation of metformin and worsened when the medication was reintroduced, suggesting a probable association between metformin and the skin manifestation 2.
A case of leukocytoclastic vasculitis was reported in a 33-year-old woman who developed palpable purpura on her lower limbs after starting metformin. The rash resolved after discontinuation and recurred with rechallenge, strongly suggesting metformin as the causative agent 3.
Three cases of photosensitivity induced by metformin have been reported, with cutaneous lesions located primarily in sun-exposed areas. The lesions healed after stopping metformin, with positive rechallenge in one case 4.
Clinical Considerations
Timing and Presentation
Metformin-associated rash can present in various forms:
- Facial rash resembling rosacea
- Palpable purpura (leukocytoclastic vasculitis)
- Photosensitivity reactions (eczematous or erythematous lesions in sun-exposed areas)
- General skin rash
Management of Metformin-Associated Rash
If a patient develops a rash while taking metformin:
- Consider metformin as a possible cause, especially if the rash developed after initiating therapy
- Evaluate for other potential causes of the rash
- Consider temporary discontinuation of metformin to assess if the rash improves
- If the rash resolves after discontinuation, consider alternative diabetes medications
- Document the reaction as a potential drug allergy
Alternative Medications
If metformin needs to be discontinued due to skin reactions, alternative glucose-lowering agents should be considered based on the patient's clinical profile:
- DPP-4 inhibitors have few side effects and minimal risk of hypoglycemia 5
- SGLT-2 inhibitors or GLP-1 receptor agonists may be appropriate, particularly for patients with cardiovascular risk factors 6
- Sulfonylureas are an option but have higher hypoglycemia risk and weight gain concerns 6
Common Side Effects of Metformin
It's important to note that gastrointestinal side effects are much more common with metformin than skin reactions:
- Diarrhea (53% vs. 12% in placebo)
- Nausea/vomiting (26% vs. 8% in placebo)
- Flatulence (12% vs. 6% in placebo)
- Abdominal discomfort (6% vs. 5% in placebo) 1
These GI side effects can often be mitigated by gradual dose titration and/or using extended-release formulations 5.
Conclusion
While metformin is generally well-tolerated and remains a cornerstone of type 2 diabetes treatment, healthcare providers should be aware that skin reactions, including various types of rash, can occur in patients taking this medication. Though less common than gastrointestinal side effects, skin manifestations should prompt consideration of metformin as a potential cause, especially when the timing of rash development correlates with medication initiation.