Effect of dipeptidyl peptidaz-4 inhibitors (dPP-4) and metformin combination on serum vitamin B12, folic acid and ferritine levels

INTRODUCTION AND OBJECTIVE: The prevalence of Type 2 Diabetes Mellitus (DM) has increased in recent years and has become an epidemic disease. The most common and first choice drug in its treatment is metformin. The most common side effects of metformin are gastrointestinal intolerance such as diarrhea and nausea. Metformin and diabetes may have an effect on vitamin B12, ferritin and folate levels in plasma. Metformin decreases vitamin B12 absorption through various mechanisms and causes vitamin B12 deficiency. In cases where hyperglycemia cannot be adequately controlled with metformin, the combination of metformin and dipeptidyl peptidase-4 inhibitor (DPP4-I) is an alternative treatment option. The aim of this study was to investigate the effect on serum vitamin B12, folic acid, and ferritin levels at baseline and 1 year later in patients using metformin and metformin-DPP4-I combination in type 2 DM patients. MATERIALS AND METHODS: Newly diagnosed type 2 DM patients who applied to our center during 2018, started metformin or metformin + DPP4-I combination, did not use any other drugs, had no chronic disease and had maximum information in the file were included in the study. Demographic data such as age and gender of the patients, and laboratory parameters such as HbA1c, vitamin B12, folate, and ferritin at the beginning and 1 year later were recorded. Statistical analysis of the data was made. RESULTS: A total of 118 patients; 59 metformin + DPP4-I and 59 metformin, who met the criteria, were included in the study. The higher number of women in the metformin group was statistically significant (p <0.001). The initial HbA1c levels between the two groups were 6.5% (1.3) in the metformin group and 8.6% (2.4) in the metformin + DPP4-I group (p= 0). Fasting plasma glucose was 131 (27) mg / dl in the metformin group and 183 (84) mg / dl in the metformin + DPP4-I combination group (p <0.001). When we look at the changes in HbA1c, vitamin B12, ferritin and folate values, which are the main objectives of the study, in the patients who received metformin and metformin + DPP4-I combination after 1 year, in the group in which metformin was started, HbA1c decreased from 6.5% (1.3) to 6.4% (1.3) and the decrease in HbA1c was not found statistically significant. HbA1c of the patients who received metformin + DPP4-I combination decreased statistically significantly from 8.6% (2.4) to 7.3% (1.2) (p <0.001). While folate decreased from 8.9 (4.8) to 8.1 (5.9) ug / L in the metformin group (p= 0.000), there was no statistical significance in the decrease in the group in which metformin + DPP4-I combination was started (p= 0.346 ). Vitamin B12 from 275 (178) to 232 (151) ng / L (p= 0.000) in the group in which metformin was started, from 309 (218) to 260 (160) ng / L in the group in which metformin + DPP4-I was started. It decreased significantly (p= 0.000). Ferritin metformin was started from 46 (83) ug / L to 38 (60.3) ug / L (p= 0.000), in the group started metformin + DPP4-I combination, 83 (121) to 66.2 (90) It decreased statistically significantly to ng / L (p= 0.002). Both metformin and metformin + DPP4I were started, so we examined the values of statistically significant decrease after 1 year in both groups. When we compared these differences between baseline and 1st year in both groups, no significant relationship was found between the two groups in vitamin B12 and ferritin reduction (vitamin B12: p = 0.346; ferritin: p = 0.379). For FPG, metformin decreased 8 (23) mg / dl in 1 year, while metformin + DPP4-I combination decreased 37 (76) mg / dl, and this difference was found to be statistically significant (p= 0.001). CONCLUSION: Serum vitamin B12 and ferritin levels decreased in both groups after 1 year. Folate dropped after 1 year only in the group that started metformin. Vitamin B12 value of patients using metformin and metformin + DPP4-I combination should be closely monitored. Ferritin can be used to predict whether the glycemic state is under control. Keywords: Diabetes mellitus, dipeptidyl peptidase-4 inhibitor, DPP4-I, metformin, folate, ferritin, vitamin B12, cobalamin