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.

A Cross Sectional Study to Assess the Prevalence of Vitamin B 12 Deficiency Among Type 2 Diabetes Mellitus Patients on Metformin Therapy in A Tertiary Care Hospital in Eastern India.

“…The mean duration of Diabetes was significantly different among the two groups in the present study implicating that patients requiring Insulin therapy had longer duration of Diabetes than patients on Metformin Monoptherapy. Almost similar findings have been documented by Kang et al 9 , where it has been shown that the patients with Metformin and Sulfonylurea combination had shorter duration of Diabetes than patients with Metformin and Insulin combination therapy. In the present study the average daily dose of Metformin was quite high(1226±450mg).…”

“…Similar findings have been echoed in the cross-sectional studies conducted separately by Kang D et al 9 and Sato et al 14 . The mean duration of Diabetes was significantly different among the two groups in the present study implicating that patients requiring Insulin therapy had longer duration of Diabetes than patients on Metformin Monoptherapy.…”

“…However, in the study conducted by Kang et al 9 there has been a statistically significant difference of HbA1C among the two groups (P<0.00). Kang et al 9 had investigated that whether Metformin in combination with Sulfonylurea causes worse deterioration of Vitamin B12 levels as compared to combination Therapy with Insulin. The study has shown in clearer terms that mean serum Vitamin B12 levels among Metformin and sulfonylurea combination group was worse as compared to Metformin Insulin group (P<0.00).…”

“…In the present study the average daily dose of Metformin was quite high(1226±450mg). Kang et al 9 has shown that 1276.16±451.2 mg mean daily Metformin dose among non-Insulin group and 1397.96±432.9 mg among the Insulin group (P=0.175). Equitable distribution of Metformin dosage among the two groups had negated any possible confounding factor in the study.The present study has also shown no statistically significant difference of glycemic control parameters among the two groups(p>0.05).…”

“…Metformin induced Viamin B12 deficiency is usually seen approximately 10-12 years of initiation of the drug. The condition is associated with decreased folate levels and increased Homocysteine and Methylmalonic Acid concentrations 9 . The exact mechanism for Metformin induced Vitamin B12 deficiency is not yet clear.…”