title: 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.
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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Kang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jae-Seung
authors.initials: JS
authors.lastname: Yun
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Ko
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Tae-Seok
authors.initials: TS
authors.lastname: Lim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yu-Bae
authors.initials: YB
authors.lastname: Ahn
authors.affiliation: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Yong-Moon
authors.initials: YM
authors.lastname: Park
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D005492:Folic Acid / Q000097:blood; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D014805:Vitamin B 12 / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000139:chemically induced* / Q000473:pathology
chemical_list: D004338:Drug Combinations; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin; D005492:Folic Acid; D014805:Vitamin B 12