Can Aspirin (acetylsalicylic acid) 81 mg daily, Atorvastatin (Lipitor) 40 mg daily, Metformin 1g twice a day (BID), Ezetimibe 10 mg daily, Vitamin B12 2500 mcg daily, Ramipril 5 mg daily, or Clopidogrel (Plavix) 75 mg daily cause numbness or tingling in the hands and feet?

Medications That Can Cause Numbness in Your Medication List

Among your medications, metformin is the most likely cause of numbness, particularly with your recent dose increase to 1g BID, as it can lead to vitamin B12 deficiency that causes peripheral neuropathy with symptoms of numbness and tingling. 1, 2

Metformin and Peripheral Neuropathy

• Metformin blocks vitamin B12 absorption in the terminal ileum, potentially causing or worsening peripheral neuropathy in patients with diabetes 2
• Long-term metformin use is associated with biochemical vitamin B12 deficiency that can lead to peripheral neuropathy, especially in patients with anemia or existing neuropathy symptoms 1
• Your recent increase to 1g BID (2g daily) puts you at higher risk, as this is the maximum effective dose where B12 deficiency is more common 1
• Risk increases significantly after 5 years of metformin use when hepatic stores of vitamin B12 become depleted 2, 3

Presentation of Metformin-Induced Neuropathy

• Typically presents as numbness and tingling in a "stocking-glove" distribution (hands and feet) 1, 4
• May include impaired vibratory sensation, proprioception, and positive Romberg test 3
• Symptoms can develop gradually and worsen with continued metformin use without B12 supplementation 2

Other Medications in Your List and Numbness

• Atorvastatin: Your recent dose increase from 10mg to 40mg could potentially cause peripheral neuropathy, though this is less common than with metformin 1
• Clopidogrel and Aspirin: These antiplatelet medications are not typically associated with numbness as a common side effect
• Ramipril: ACE inhibitors like ramipril are not commonly associated with peripheral neuropathy 1
• Ezetimibe: Not typically associated with peripheral neuropathy
• Vitamin B12 supplementation: Your current supplementation (2500 mcg daily) is actually protective against neuropathy, not causative 1

Management Recommendations

1. Continue vitamin B12 supplementation at your current dose of 2500 mcg daily, as this may help counteract metformin-induced B12 deficiency 1, 2

2. Request laboratory testing for:

   • Serum vitamin B12 levels
   • If B12 levels are borderline, methylmalonic acid and homocysteine levels can detect early B12 deficiency 2

3. Neurological assessment to evaluate:

   • Small-fiber function (pinprick and temperature sensation)
   • Large-fiber function (vibration perception and 10-g monofilament)
   • Protective sensation (10-g monofilament) 1

4. Consider metformin dose adjustment if neuropathy is confirmed and attributed to B12 deficiency 2

Important Considerations

• Diabetic peripheral neuropathy and metformin-induced B12 deficiency neuropathy can present similarly, making diagnosis challenging 1
• With adequate vitamin B12 replacement, symptoms may stabilize but objective findings of neuropathy often do not completely improve 2
• Paradoxically, some research suggests metformin may have protective effects against certain types of neuropathic pain, highlighting the complex relationship between metformin and neurological symptoms 5, 6, 7

When to Seek Immediate Medical Attention

• If numbness is accompanied by weakness, severe pain, or rapid progression of symptoms
• If numbness affects your balance or ability to perform daily activities 3
• If you experience symptoms of severe B12 deficiency such as confusion, memory problems, or difficulty walking 1, 3