Vitamin B12 deficiency in long-term metformin use and clinician awareness: a scoping review

Background: Metformin is the first-line treatment for type 2 diabetes mellitus (T2DM). Long-term use of metformin has been associated with vitamin B12 deficiency, which may lead to serious complications such as anaemia and neuropathy. Although international bodies have recommended screening for vitamin B12 deficiency in patients on long-term metformin, it is unclear how aware clinicians are of this adverse effect and to what extent such guidance is being followed in practice.

Methods: A scoping review was conducted using Joanna Briggs Institute (JBI) methodology. Databases searched included MEDLINE, Medical Literature Analysis and Retrieval System Online (PubMed), British Nursing Index (BNI), Google Scholar, Cochrane, Embase, Web of Science and CINAHL, Cumulative Index to Nursing and Allied Health Literature (EBSCO) alongside searching for grey literature such as EThOS (Electronic Theses Online Service), DART (Digital Access to Research Theses) European and Kings College London Research Portal. Studies published in English from 1990 onwards were included if they addressed clinician awareness or screening practices. Data were extracted and summarised using a structured tool, with themes mapped visually. The literature search was conducted between 1 August 2025 and 1 November 2025 and included studies published from January 1990 onwards.

Results: 23 sources were included in the review. 7 studies directly assessed clinician awareness of metformin-associated vitamin B12 deficiency, all conducted outside the UK. Across 15 studies reporting screening practices, routine vitamin B12 monitoring was uncommon, with annual testing rates in general below 20% of eligible patients (range 2.6%–19.8%). In a large retrospective cohort study of patients on long-term metformin, 44.9% underwent vitamin B12 testing, with a mean delay of 990 days from treatment initiation. Screening was predominantly symptom-triggered rather than preventive, and older adults and other high-risk groups were consistently less likely to be tested. Reported barriers included lack of clinical prompts, competing priorities and testing costs.

Conclusions: Clinician awareness of the link between long-term metformin use and vitamin B12 deficiency is present but inconsistently translated into practice. Screening practices remain suboptimal despite recent guideline updates. Interventions, such as checklists, prompts and updated training, may support improved adherence. However, no UK-based studies were identified, highlighting a gap in national evidence. Routine, risk-based screening in primary care could prevent significant morbidity associated with undiagnosed vitamin B12 deficiency in this population.