From the Guidelines
Metformin commonly causes vitamin B12 deficiency, and long-term use can reduce vitamin B12 absorption in the intestines by interfering with calcium-dependent mechanisms needed for B12 uptake. This deficiency typically develops gradually over months to years of metformin use, with studies suggesting that 10-30% of patients on long-term metformin therapy may develop low B12 levels 1. The risk increases with higher metformin doses and longer duration of treatment. Symptoms of B12 deficiency include:
- Fatigue
- Weakness
- Numbness or tingling in hands and feet
- Difficulty walking
- Memory problems
- Anemia
Healthcare providers often recommend regular B12 level monitoring for patients on metformin, particularly after 1-2 years of use. Many doctors suggest B12 supplementation (typically 1000 mcg daily or weekly) for patients on long-term metformin therapy, even without confirmed deficiency, as a preventive measure. Patients taking metformin should discuss B12 monitoring and potential supplementation with their healthcare provider. According to the most recent study 1, metformin use is associated with increased risk of vitamin B12 deficiency and worsening of symptoms of neuropathy, suggesting periodic testing of vitamin B12 levels.
From the FDA Drug Label
In metformin hydrochloride tablets clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients Such decrease, possibly due to interference with B 12 absorption from the B 12-intrinsic factor complex, may be associated with anemia but appears to be rapidly reversible with discontinuation of metformin hydrochloride tablets or vitamin B 12 supplementation Certain individuals (those with inadequate vitamin B 12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B 12 levels. Measure hematologic parameters on an annual basis and vitamin B 12 at 2 to 3 year intervals in patients on metformin hydrochloride tablets and manage any abnormalities [see Adverse Reactions ( 6.1) ].
The vitamin deficiency that comes with metformin is Vitamin B12 Deficiency. Patients on metformin should have their hematologic parameters measured annually and their vitamin B12 levels measured every 2 to 3 years to manage any abnormalities 2, 2.
From the Research
Vitamin Deficiency Associated with Metformin
- The vitamin deficiency most commonly associated with metformin is vitamin B12 deficiency, as reported in multiple studies 3, 4, 5, 6, 7.
- Vitamin B12 plays a critical role in DNA synthesis and neuroprotection, and its deficiency can lead to hematologic abnormalities, progressive axonal demyelination, and peripheral neuropathy 3.
Risk Factors for Vitamin B12 Deficiency
- Long-term and high-dose metformin therapy has been shown to impair vitamin B12 status, increasing the risk of deficiency 3, 4, 5.
- The risk of vitamin B12 deficiency also increases with the duration of metformin use, with a significant association found between years of metformin use and increased risk of B12 deficiency 5.
- Patient age and ethnicity may also be risk factors for vitamin B12 deficiency in metformin users, although further research is needed to confirm this 4.
Clinical Implications and Management
- Vitamin B12 deficiency can have serious clinical consequences, including anemia and peripheral neuropathy, and routine testing of vitamin B12 levels in metformin-treated patients should be considered 5, 6.
- Early detection and supplementation of vitamin B12 are crucial to prevent adverse outcomes in patients taking metformin 6.
- Healthcare professionals should be aware of the association between metformin use and vitamin B12 deficiency and take steps to monitor and manage vitamin B12 levels in patients using metformin 6, 7.