Can metformin, acarbose, fenofibrate, amlodipine, or Symbicort cause hypovitaminosis D?

Metformin and Vitamin B12 Deficiency: The Only Established Association

Among the medications you listed (metformin, acarbose, fenofibrate, amlodipine, and Symbicort), only metformin is associated with vitamin deficiency—specifically vitamin B12 deficiency, not vitamin D deficiency. None of these medications cause vitamin D levels to drop below 3 ng/mL (or any clinically significant vitamin D deficiency). 1

Metformin and Vitamin B12 (Not Vitamin D)

Metformin causes vitamin B12 deficiency, not vitamin D deficiency:

• Long-term metformin use is associated with biochemical vitamin B12 deficiency, with risk increasing significantly after 4-5 years of continuous therapy 1, 2
• The American Diabetes Association recommends periodic measurement of vitamin B12 levels in all metformin-treated patients, especially those with anemia or peripheral neuropathy 1
• Annual monitoring should be considered for patients on metformin for more than 4 years 2
• Vitamin B12 deficiency is defined as levels <150 pmol/L or ≤203 pg/mL 1, 2

Metformin does NOT cause vitamin D deficiency:

• A randomized placebo-controlled trial (HOME trial) with 390 insulin-treated patients followed for 52 months found that metformin had no effect on vitamin D (25-hydroxyvitamin D) levels 3
• A retrospective study of 706 patients with type 2 diabetes confirmed no statistically significant difference in vitamin D levels between metformin users and non-users 4
• Metformin does not negatively affect treatment of vitamin D deficiency in patients with diabetes 4

The Other Medications

None of the other medications you listed (acarbose, fenofibrate, amlodipine, or Symbicort) are associated with causing vitamin D or vitamin B12 deficiency in the medical literature or guidelines provided.

Clinical Pitfall to Avoid

The confusion likely stems from metformin's well-established association with vitamin B12 deficiency being mistakenly attributed to vitamin D. These are completely different vitamins with different mechanisms:

• Vitamin B12 deficiency from metformin occurs through interference with calcium-dependent binding of the intrinsic factor-B12 complex in the terminal ileum 5
• Vitamin D deficiency in diabetic patients is common but related to other factors such as inadequate intake, limited sun exposure, obesity, and winter season—not metformin use 6, 3, 4

What You Should Monitor

If your patient is on metformin:

• Monitor vitamin B12 levels periodically, especially after 4 years of use 1, 2
• Check more frequently if the patient has anemia, peripheral neuropathy, is vegan, or has had gastric/small bowel surgery 2
• Consider prophylactic calcium and vitamin B12 supplements in high-risk patients 5