Impact of the MHRA Safety Update on Vitamin B 12 Testing and Coding in Metformin Users: A Retrospective Primary Care Analysis

Abstract Background: Metformin is the most commonly prescribed first-line oral treatment for type 2 diabetes mellitus (T2DM) in the UK. Long-term therapy has been linked to vitamin B₁₂ deficiency, a concern recognised for decades but not consistently addressed. In June 2022, the UK Medicines and Healthcare products Regulatory Agency (MHRA) classified low vitamin B₁₂ levels as a common adverse effect of metformin and advised clinicians to consider periodic testing in at-risk patients. Translating such regulatory advice into routine practice can be challenging, and the extent to which the MHRA guidance has influenced testing and diagnostic coding for vitamin B₁₂ deficiency in primary care remains unclear. This study evaluated trends in vitamin B₁₂ testing and deficiency coding in metformin-treated patients compared with the general population before and after the 2022 MHRA Drug Safety Update. Methods: A retrospective quantitative analysis was conducted using Read code data from 148,000 electronic medical records across three Primary Care Networks (PCNs) in the Southwest of England. Vitamin B₁₂ testing and deficiency coding rates were compared in patients prescribed metformin and the general population across two periods: pre-guidance (2017–2021) and post-guidance (2022–2024). Welch’s t-tests were used to determine statistical significance, with p < 0.05 considered significant. Results: Among patients prescribed metformin, vitamin B₁₂ testing rates rose from 34.5% (SD = 1.8) pre-guidance to 38.2% (SD = 0.4) post-guidance (p = 0.008). In the general population, testing rates also increased from 12.2–14.7% (p = 0.009). However, coding for vitamin B₁₂ deficiency remained unchanged at 0.25% in the metformin group and decreased slightly from 0.072–0.060% in the general population, with no statistically significant difference (p = 0.997 and p = 0.348 respectively). Conclusions: This study demonstrated that the release of the MHRA Drug Safety Update was associated with a modest (4% increase overall) but statistically significant increase in vitamin B₁₂ testing in patients prescribed metformin. However, diagnostic coding practices did not change, suggesting limited translation of safety alerts into structured documentation. Further research is warranted to explore barriers to implementation and evaluate interventions aimed at improving monitoring and coding compliance in primary care.