Is there a relationship between metformin-related gastrointestinal symptoms and vitamin B12 deficiency in patients with type 2 diabetes mellitus?

Abstract

Metformin (MTF) associated gastrointestinal symptoms are fairly common side effects that adversely affect patients' treatment adherence. However, the variability of gastrointestinal symptoms in MTF-using patients has not been fully explained. In our study, we aimed to investigate the relationship between vitamin B12 deficiency with MTF-related gastrointestinal symptoms. Patients with type 2 diabetes mellitus (T2DM) using MTF were included in the study sequentially. Demographic characteristics of the patients, duration of diabetes, MTF dose and duration used, and gastrointestinal symptoms were recorded. Afterward, a hemogram, HgbA1c, and vitamin B12 measurements were performed. Patients with and without vitamin B12 deficiency were divided into two groups. The two groups were compared with statistical methods. Twenty-five percent of patients had low serum vitamin B12 levels. Patients with vitamin B12 deficiency had a longer diabetes duration, and a longer MTF usage duration (p<0.001, p<0.001) than the patients without vitamin B12 deficiency. There was no correlation between B12 deficiency and MTF dosage (p=0.590). Gastrointestinal symptoms were seen more frequently in the B12 deficiency group (p=0.025). Bloating and constipation, nausea, abdominal pain, and vomiting were seen commonly in the B12 deficiency group (p=0.002, p<0.001, p=0.014, p=0.004, respectively). Three or more symptoms were frequently seen in B12-deficient patients (p<0.001). Patients with both a MTF usage duration of 10 years or higher and vitamin B12 deficiency are found to be 434% more likely to have active gastrointestinal symptoms than all other patient groups (OR:5.343, 95%CI (2.173-13.140), p<0.001). Study results have shown that gastrointestinal symptoms seen in patients with T2DM taking MTF may be associated with vitamin B12 deficiency. MTF-related gut microbiome changes may play a role in this relationship. In particular, we recommend that patients who have been using MTF for ≥10 years and have gastrointestinal complaints should be followed more closely for vitamin B12 deficiency.