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Observational Study
. 2018 Oct 15;13(10):e0204420.
doi: 10.1371/journal.pone.0204420. eCollection 2018.

The Association of Metformin Use With Vitamin B12 Deficiency and Peripheral Neuropathy in Saudi Individuals With Type 2 Diabetes Mellitus

Free PMC article
Observational Study

The Association of Metformin Use With Vitamin B12 Deficiency and Peripheral Neuropathy in Saudi Individuals With Type 2 Diabetes Mellitus

Turki J Alharbi et al. PLoS One. .
Free PMC article


Aims: To compare the prevalence of vitamin B12 deficiency and peripheral neuropathy between two groups of type 2 diabetes mellitus (T2DM) patients treated with or without metformin, and to determine factors associated with vitamin B12 deficiency therapy and dietary intake of vitamin B12.

Methods: In this retrospective study, we recruited 412 individuals with T2DM: 319 taking metformin, and 93 non-metformin users. Demographics, dietary assessment for vitamin B12 intakes, and medical history were collected. Participants were assessed for peripheral neuropathy. Blood specimens were collected and checked for serum vitamin B12 levels. The differences between the two groups were analyzed using an independent t-test for continuous data, and the Chi-squared or Fisher's exact test was used for categorical data. The relationship of vitamin B12 deficiency with demographics and clinical characteristics was modeled using logistic regression.

Results: The prevalence of B12 deficiency was 7.8% overall, but 9.4% and 2.2% in metformin users and non-metformin users, respectively. The odds ratio for serum vitamin B12 deficiency in metformin users was 4.72 (95% CI, 1.11-20.15, P = 0.036). There were no significant differences in a test of peripheral neuropathy between the metformin users and non-metformin users (P > 0.05). Low levels of vitamin B12 occurred when metformin was taken at a dose of more than 2,000 mg/day (AOR, 21.67; 95% CI, 2.87-163.47) or for more than 4 years (AOR, 6.35; 95% CI, 1.47-24.47).

Conclusion: Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (> 2,000 mg/day) and for a longer duration (> 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.

Conflict of interest statement

The authors have declared that no competing interests exist.


Fig 1
Fig 1. Prevalence of neuropathy in the metformin and non-metformin groups, based on the Toronto Clinical Scoring System.
Fig 2
Fig 2. Prevalence of neuropathy, as assessed by the focused neurological test (N = 412).
Fig 3
Fig 3. Non-parametric LOWESS curve with a scatter plot for the relationship between the average weekly vitamin B12 consumption and serum vitamin B12 (N = 412).

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This study was funded internally by the Family and Community Medicine Department at the PSMMC. There is no source of external funding.