“Frequency of Vitamin B12deficiency in Metformin-Treated type 2 Diabetic Patients”

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by insulin resistance and relative insulin deficiency. Metformin, a first-line pharmacological treatment for T2DM, is highly effective in glycaemic control but has been associated with Vitamin B12 deficiency, particularly in long-term and high-dose therapy. Vitamin B12 is critical for neurological function, DNA synthesis, and red blood cell production. Its deficiency can exacerbate complications such as neuropathy, anaemia, and cognitive impairments, which are already common in diabetic patients. This study investigates the prevalence and impact of Vitamin B12 deficiency among T2DM patients receiving metformin therapy at different dosages.

Methodology: This cross-sectional observational study was conducted in the Department of General Medicine and Endocrinology at the National Institute of Medical Sciences & Research, Jaipur, over 18 months. The study included 155 T2DM patients treated with metformin for at least six months. Participants were divided into two groups based on their metformin dosage: 500 mg and 1000 mg daily. Exclusion criteria included Type 1 diabetes, pregnancy, bariatric surgery, inflammatory bowel disease, chronic kidney or liver disease, and recent Vitamin B12 supplementation.

Blood samples were collected to measure Random Blood Sugar (RBS), Glycated Hemoglobin (HbA1c), and serum Vitamin B12 levels using chemiluminescent assays. Data were analyzed using SPSS software, with a p-value of <0.05 considered statistically significant. Comparative analysis was performed to evaluate Vitamin B12 levels between the dosage groups.

Results: The study population consisted of 155 patients, evenly distributed across the two metformin dosage groups (500 mg: 77, 1000 mg: 78). The mean age of participants was 60.338 ± 5.183 years (500 mg) and 60.795 ± 4.338 years (1000 mg). Gender distribution was balanced, with no significant differences in anthropometric measures or smoking status.

Laboratory analysis revealed no significant differences in RBS (p = 0.827) or HbA1c levels (p = 0.364) between the two groups, indicating comparable glycaemic control. However, a significant difference was observed in serum Vitamin B12 levels. Patients in the 1000 mg group exhibited lower mean Vitamin B12 levels (312.474 ± 223.979 pg/mL) compared to the 500 mg group (406.753 ± 309.793 pg/mL), with a p-value of 0.031.

The results suggest that higher doses of metformin are associated with a greater risk of Vitamin B12 deficiency. This finding aligns with existing literature, which highlights metformin’s impact on gut microbiota and its interference with the ileal absorption of Vitamin B12.

Conclusion: This study confirms a dose-dependent association between metformin therapy and reduced Vitamin B12 levels in T2DM patients. While metformin remains a cornerstone in diabetes management due to its efficacy and safety, its potential to induce Vitamin B12 deficiency requires attention. Routine monitoring of Vitamin B12 levels is essential, particularly for patients on high-dose or long-term therapy.

Proactive screening and timely supplementation with oral or intramuscular Vitamin B12 can prevent complications such as neuropathy, anaemia, and cognitive impairments, thereby improving patient outcomes and quality of life. Further research is needed to explore strategies for mitigating this risk, including fortifying metformin formulations with Vitamin B12 or developing alternative therapies with fewer nutritional side effects.