Assessment of vitamin B₁₂deficiency and B₁₂screening trends for patients on metformin: a retrospective cohort case review

Abstract

ObjectivesOur study investigated the use of vitamin B12 testing in a large cohort of patients on metformin and assesses appropriateness and benefits of screening recommendations for vitamin B12 deficiency.DesignThis retrospective cohort study included insured adult patients who had more than 1 year of metformin use between 1 January 2010 and 1 October 2016 and who filled at least two consecutive prescriptions of metformin to establish compliance. The comparison group was not exposed to metformin. Primary outcome was incidence of B12 deficiency diagnosed in patients on metformin. Secondary outcome was occurrence of B12 testing in the patient population on metformin. Records dated through 31 December 2018 were analysed.SettingLarge hospital system consisting of inpatient and outpatient data base.ParticipantsA diverse, adult, insured population of patients who had more than 1 year of metformin use between 1 January 2010 and 1 October 2016 and who filled at least two consecutive prescriptions of metformin.ResultsOf 13 489 patients on metformin, 6051 (44.9%) were tested for vitamin B12 deficiency, of which 202 (3.3%) tested positive (vs 2.2% of comparisons). Average time to test was 990 days. Average time to test positive for deficiency was 1926 days. Factors associated with testing were linked to sex (female, 47.8%), older age (62.79% in patients over 80 years old), race (48.98% white) and causes of malabsorption (7.11%). Multivariable logistic regression showed older age as the only factor associated with vitamin B12 deficiency, whereas African-American ethnicity approached significance as a protective factor.ConclusionsBased on our study’s findings of vitamin B12 deficiency in patients on metformin who are greater than 65 years old and have been using it for over 5 years, we recommend that physicians consider screening in these populations.

Long-term metformin therapy and vitamin B12 deficiency: an association to bear in mind

“…A recent retrospective study conducted in a large cohort of adult patients ( n = 13489) who had received metformin for more than 1 year aimed to assess the appropriateness and benefits of screening recommendations for vitamin B12 deficiency[ 47 ]. The mean time between metformin initiation and incidence of vitamin B12 deficiency was 5.3 years.…”

“…These results suggest that patients who have been using metformin for more than 5 years and patients older than 65 are at increased risk for vitamin B12 deficiency. Therefore, authors concluded that screening for vitamin B12 deficiency might be considered in such populations even if they are asymptomatic for the deficiency[ 47 ].…”

Nutraceutical Treatment of Patients with Polycystic Ovary Syndrome

“…Patients suffering from PCOS are at risk of long-term negative health hazards that are not, or only partly addressed by the usual allopathic treatments, the adherence to which is suboptimal in real-world [33]. In addition, Metformin may induce Vitamin B12 deficiency [34]. The mechanisms underlying PCOS-associated health hazards must be targeted and corrected, in order to improve the wellbeing of patients and to reduce the probability of ill-health when aging.…”

Metformin‐induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes

“…32 Similar results were obtained in studies from Korea, 33 Brazil 34 and the USA. 35 In addition, a nested case-control study from Hong Kong showed that for each 1-g dose of metformin that was being utilized there was a 2.88-fold (95% CI 2.15-3.87, p = 0001) increase in vitamin B12 deficiency and in those utilizing metformin for over 3 years a 2.39-fold increase (95% CI 1.46-3.91, p = 0.001). 36 Similarly, case reports have described low serum vitamin B12 levels being associated with metformin use.…”