Higher prevalence of metformin-induced vitamin B12 deficiency in sulfonylurea combination compared with insulin combination in patients with type 2 diabetes: a cross-sectional study.

Donghoon Kang,Sun-Hye Ko,Yong-Moon Park,Tae-Seok Lim,Yu-Bae Ahn,Seung-Hyun Ko,Jae-Seung Yun,Yu Wang

doi:10.1371/journal.pone.0109878

Donghoon Kang, Sun-Hye Ko + Show 6 more

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https://doi.org/10.1371/journal.pone.0109878

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Journal: PloS one	Publication Date: Oct 9, 2014
Citations: 49	License type: CC BY 4.0

Affiliation: St. Vincent's Hospital

Abstract

Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes. We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period. A total of 394 patients with type 2 diabetes treated with metformin and sulfonylurea (S+M group, n = 299) or metformin and insulin (I+M group, n = 95) were consecutively recruited. The vitamin B12 and folate levels were quantified using the chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12≤300 pg/mL without folate deficiency (folate>4 ng/mL). The mean age of and duration of diabetes in the subjects were 59.4±10.5 years and 12.2±6.7 years, respectively. The mean vitamin B12 level of the total population was 638.0±279.6 pg/mL. The mean serum B12 levels were significantly lower in the S+M group compared with the I+M group (600.0±266.5 vs. 757.7±287.6 pg/mL, P<0.001). The prevalence of vitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001). After adjustment for various factors, such as age, sex, diabetic duration, duration or daily dose of metformin, diabetic complications, and presence of anemia, sulfonylurea use was a significant independent risk factor for B12 deficiency (OR = 4.74, 95% CI 1.41–15.99, P = 0.012). In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.

Highlights

Metformin, which belongs to the biguanide class, is one of the most generally used oral hypoglycemic agents
299 patients were treated with metformin combined with sulfonylurea (S+M group), and 95 patients were treated with metformin and insulin (I+M group)
Higher prevalence of vitamin B12 deficiency in patients with type 2 diabetes compared with that found for the insulin plus metformin combination therapy

Summary

Introduction

Metformin, which belongs to the biguanide class, is one of the most generally used oral hypoglycemic agents. It has been used for more than 50 years and was approved by the US Food and Drug Administration (FDA) in 1994 [1]. Many clinical practice guidelines for patients with type 2 diabetes, including the American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD), and the Korean Diabetes Association (KDA), recommend that metformin treatment should begin at the time of diagnosis of diabetes with lifestyle modification in the absence of contraindications [2,3,4]. According to data using the IMS Health National Disease and Therapeutic Index of the U.S, more than 50% of treatment visits before 2012 were associated with metformin [5]

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