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Background
Vitamin B12 deficiency is common in the elderly population and can cause severe complications. The use of certain medication has in previous studies been associated with vitamin B12 deficiency in the general population. To identify elderly patients at risk for vitamin B12 deficiency due to medication use, we evaluated the association between medication use and vitamin B12 deficiency in the elderly population.
Methods
Hospitalized geriatric patients 65 years of age or over with a serum vitamin B12 measurement within one week of the admittance date were included. Patients were classified as either B12 normal (258–635 pmol/L) or B12 deficient (< 148 pmol/L). Upon hospital admission patients’ medication use was verified. The association between vitamin B12 deficiency and the use of antacid, antiepileptic, antidiabetic, lipid lowering and other medication was evaluated by univariate and multivariate analyses.
Results
Of the 7132 patients included in the study, 532 (7.5%) had vitamin B12 deficiency and 3433 (48.1%) patients had normal vitamin B12 concentrations. Metformin use was significantly and independently (adjusted OR 2.5; 95% CI 1.7–3.6) associated with a dose-dependent higher risk of vitamin B12 deficiency. The use of other medication evaluated in this study was not associated with vitamin B12 deficiency.
Conclusions
Metformin use is significantly associated with vitamin B12 deficiency in the elderly, and this risk rises with higher metformin doses. Monitoring and timely start of vitamin B12 supplementation along with the lowest possible metformin dose are essential to prevent complications.
Importance: Preclinical and preliminary human evidence suggests that metformin, a first-line treatment for type 2 diabetes, reduces inflammation, preserves cartilage, and improves knee pain in knee osteoarthritis.
Objective: To evaluate the effects of metformin on knee pain at 6 months in participants with symptomatic knee osteoarthritis and overweight or obesity.
Design, setting, and participants: Community-based randomized, parallel-group, double-blind, placebo-controlled clinical trial that used telemedicine to recruit and follow up participants remotely. Individuals with knee pain for 6 months or longer, a pain score greater than 40 mm on a 100-mm visual analog scale (VAS), and body mass index of 25 or higher were recruited from the community through local and social media advertisements in Victoria, Australia, between June 16, 2021, and August 1, 2023. Final follow-up occurred on February 8, 2024.
Interventions: Participants were randomly assigned to receive either oral metformin, 2000 mg/d (n = 54), or identical placebo (n = 53) for 6 months.
Main outcomes and measures: The primary outcome was change in knee pain, measured using a 100-mm VAS (score range, 0-100; 100 = worst; minimum clinically important difference = 15) at 6 months.
Results: Of 225 participants assessed for eligibility, 107 (48%) were randomized (mean age, 58.8 [SD, 9.5] years; 68% female) and assigned to receive metformin or placebo. Eighty-eight participants (82%) completed the trial. At 6 months, the mean change in VAS pain was -31.3 mm in the metformin group and -18.9 mm in the placebo group (between-group difference, -11.4 mm; 95% CI, -20.1 to -2.6 mm; P = .01), corresponding to an effect size (standardized mean difference) of 0.43 (95% CI, 0.02-0.83). The most common adverse events were diarrhea (8 [15%] in the metformin group and 4 [8%] in the placebo group) and abdominal discomfort (7 [13%] in the metformin group and 5 [9%] in the placebo group).
Conclusions and relevance: These results support use of metformin for treatment of symptomatic knee osteoarthritis in people with overweight or obesity. Because of the modest sample size, confirmation in a larger clinical trial is warranted.
Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman's correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.
