Relationship between metformin use and vitamin B<sub>12 </sub>status in patients with type 2 diabetes in Japan

Sugawara, Kenji; Okada, Yuko; Sakaguchi, Kazuhiko; Ogawa, Wataru

doi:10.1111/jdi.13200

Cited by 10 publications

(14 citation statements)

References 28 publications

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“…Thus, the Hb levels of both groups did not show a statistical difference. Therefore, BG did not cause anemia in the patients of this study, which conforms to the results of other studies in Japan [5].…”

Section: Study 1 Bg Did Not Cause Anemiasupporting

confidence: 92%

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Angiotensin receptor blockers significantly reduce hemoglobin level in patients with type 2 diabetes mellitus not suffered chronic cardiac failure and chronic kidney disease

et al. 2021

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Anemia due to angiotensin receptor blocker (ARB) therapy has been previously reported in patients with diabetes mellitus with glomerular filtration rates of <60 mL min -1 /1.73 m 2 . However, whether Japanese patients with type 2 diabetes mellitus (T2DM) receiving ARB therapy for chronic cardiac failure and chronic kidney disease develop reduced hemoglobin (Hb) levels has not been elucidated. Thus, this cross-sectional study was conducted, and Hb levels were compared between patients with T2DM with and without ARB administration. No significant difference in the prescribed proportion of antidiabetic medicines such as biguanide, sodium glucose co-transporter 2 inhibitors, and α-glucosidase inhibitors was found between the group treated with ARBs and the group without ARBs. Thus, we considered that the effects of antidiabetic medicines on the results were minimum. In this study, the Hb levels of patients who received ARBs (13.8 ± 1.7 g/dL) were significantly lower than those of patients without ARBs (14.9 ± 1.35 g/dL) (p = 0.034). The difference between this study and a previous study relies on eGFR levels. Thus, the eGFR levels of the patients in this study and the previous study were above 60 and below 60 mL min -1 /1.73 m 2 , respectively. Despite those differences, both studies showed that the use of ARBs was associated with a decrease in Hb levels in patients with T2DM. Thus, the evaluation of glycated Hb levels should be focused on whether ARBs are prescribed for patients with T2DM.

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Section: Study 1 Bg Did Not Cause Anemiasupporting

confidence: 92%

“…Study 1. BG caused anemia by disrupting vitamin B12 absorption in foreign countries [4] but did not seem to cause anemia in Japan [5]. This discrepancy was investigated by confirming whether BG causes anemia in the patients assessed in this study.…”

Section: Methodsmentioning

confidence: 70%

Angiotensin receptor blockers significantly reduce hemoglobin level in patients with type 2 diabetes mellitus not suffered chronic cardiac failure and chronic kidney disease

et al. 2021

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“…The study was conducted in a population that was taking approximately 1000 mg of metformin, which is equivalent to the average dose in Japan. 36 In addition, the study followed a 52-week course based on the consideration that this was sufficiently long to reveal the long-term course of the drug. In fact, results of the evaluation differed between 24 and 52 weeks.…”

Section: Discussionmentioning

confidence: 99%

A 52‐week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N‐ISM study

Kitazawa

Kubo²,

Suzuki

et al. 2021

Diabetes Obesity Metabolism

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Aim To compare the long‐term efficacy of sodium‐glucose co‐transporter‐2 inhibitors and dipeptidyl peptidase‐4 inhibitors as second‐line drugs after metformin for patients not at high risk of atherosclerotic cardiovascular disease (ASCVD). Materials and methods In a 52‐week randomized open‐label trial, we compared ipragliflozin and sitagliptin in Japanese patients diagnosed with type 2 diabetes, without prior ASCVD and treated with metformin. The primary endpoint was a glycated haemoglobin (HbA1c) reduction of ≥0.5% (5.5 mmol/mol) without weight gain at 52 weeks. Results Of a total of 111 patients (mean age 59.2 years, mean body mass index [BMI] 26.6 kg/m2, 61.3% men), 54 patients received ipragliflozin and 57 received sitagliptin. After 52 weeks, achievement of the primary endpoint was not significantly different (37.0% and 40.3%; P = 0.72). HbA1c reduction rate at 24 weeks was greater for sitagliptin (56.1%) than for ipragliflozin (31.5%; P = 0.01). From 24 to 52 weeks, the HbA1c reduction with sitagliptin was attenuated, with no significant difference in HbA1c reduction after 52 weeks between sitagliptin (54.4%) and ipragliflozin (38.9%; P = 0.10). Improvements in BMI, C‐peptide and high‐density lipoprotein cholesterol were greater with ipragliflozin than with sitagliptin. Adverse events occurred in 17 patients with ipragliflozin and in 10 patients with sitagliptin (P = 0.11). Conclusion The HbA1c‐lowering effect at 24 weeks was greater with sitagliptin than with ipragliflozin, but with no difference in efficacy related to HbA1c and body weight at 52 weeks. However, some ASCVD risk factors improved with ipragliflozin.

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“…Taking metformin may cause vitamin B12 deficiency and it is associated with anemia in the elderly. [16][17][18][19][20] And, long-term use of metformin increased the Hcy level in patients with type 2 diabetes and cardiovascular disease. 11 Increased concentrations of Hcy are a well-known risk factor for coronary heart disease and stroke.…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that the level of homocysteine in diabetic patients is positively correlated with the daily dose of metformin. Taking metformin may cause vitamin B12 deficiency and it is associated with anemia in the elderly 16–20 . And, long‐term use of metformin increased the Hcy level in patients with type 2 diabetes and cardiovascular disease 11 .…”

Section: Introductionmentioning

confidence: 99%

The effect of metformin on homocysteine levels in patients with polycystic ovary syndrome: A systematic review and meta‐analysis

Fang

Yang

et al. 2021

J of Obstet and Gynaecol

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Purpose Metformin is widely used as an insulin sensitizer in polycystic ovary syndrome (PCOS) patients. However, previous studies have found that the effect of metformin on the level of homocysteine were not consistent in PCOS patients. The aim of this review was to analyze the effect of metformin on homocysteine levels in patients with PCOS patients. Methods The Cochrane Library, Pubmed, and Web of Science were searched according to predefined search terms. There is no restriction for publication time and language. Results Eleven studies were included and the data were extracted. The homocysteine level in PCOS patients was significantly increased after taking metformin (mean difference [MD] −1.33; 95% confidence interval [CI] −2.16 to −0.49, p = 0.002). Subgroup analysis showed that the level of homocysteine was generally increased in PCOS patients with body mass index (BMI) ≥25 after taking metformin alone (MD −1.82; 95% CI −2.56 to −1.07, p < 0.00001). There was no significant change in homocysteine level in PCOS patients with BMI <25 (MD 0.69; 95% CI −0.41 to 1.79, p = 0.22). Subgroup analysis showed that there was no significant difference when taking metformin >3 months or taking metformin ≤3 months (p = 0.84). Taking metformin ≥1700 mg/days significantly increased homocysteine levels in PCOS patients (MD −2.05; 95% CI −2.40 to −1.70, p < 0.00001). When taking metformin <1700 mg/days, there was no significant difference in homocysteine level in PCOS patients (MD 0.15; 95% CI −1.06 to 1.37, p = 0.80). The difference between the two subgroups was significant (p = 0.0006). There was no significant difference in vitamin B12 level before and after metformin treatment (MD 24.70; 95% CI −22.54 to 71.93, p = 0.31). There was a decrease in serum folic acid level after metformin administration (MD 1.03; 95% CI 0.80 to 1.26, p < 0.00001). Conclusion Taking metformin alone increased homocysteine levels and decreased folic acid levels in nonpregnant PCOS patients. And, it was suggested that the dosage of metformin should be less than 1700 mg/days. The supplement of folic acid and B vitamins during metformin administration may be essential in nonpregnant PCOS patients. We should pay much attention to the potential effect of metformin in PCOS patients.

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Relationship between metformin use and vitamin B₁₂status in patients with type 2 diabetes in Japan

Cited by 10 publications

References 28 publications

Angiotensin receptor blockers significantly reduce hemoglobin level in patients with type 2 diabetes mellitus not suffered chronic cardiac failure and chronic kidney disease

Angiotensin receptor blockers significantly reduce hemoglobin level in patients with type 2 diabetes mellitus not suffered chronic cardiac failure and chronic kidney disease

A 52‐week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N‐ISM study

The effect of metformin on homocysteine levels in patients with polycystic ovary syndrome: A systematic review and meta‐analysis

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Relationship between metformin use and vitamin B12 status in patients with type 2 diabetes in Japan

Cited by 10 publications

References 28 publications

Angiotensin receptor blockers significantly reduce hemoglobin level in patients with type 2 diabetes mellitus not suffered chronic cardiac failure and chronic kidney disease

Angiotensin receptor blockers significantly reduce hemoglobin level in patients with type 2 diabetes mellitus not suffered chronic cardiac failure and chronic kidney disease

A 52‐week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N‐ISM study

The effect of metformin on homocysteine levels in patients with polycystic ovary syndrome: A systematic review and meta‐analysis

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Relationship between metformin use and vitamin B₁₂status in patients with type 2 diabetes in Japan