High Frequency of Defecation under Metformin Use May Be a Potential Glucose-lowering Factor Independent of the Dose-dependent Effect of Metformin in Patients with Type 2 Diabetes Mellitus.

Objective Our previous study indicated that the efficacy of metformin in lowering glycated hemoglobin (HbA1c) levels may be influenced by the pretreatment frequency of defecation (FD) in patients with type 2 diabetes mellitus (T2DM). This study aimed to further examine how FD and the metformin dose may affect HbA1c changes (ΔHbA1c) in T2DM patients. Methods A retrospective analysis was conducted on inpatients who received antidiabetic treatment without altering dosages for six months post-discharge, except for minor insulin adjustments. For new patients, FD was assessed before (pretreatment FD) and after the initiation of antidiabetic therapy (posttreatment FD). For patients already on treatment, FD was evaluated during hospitalization (posttreatment FD). Patients were categorized based on their metformin use, and the relationship between FD and ΔHbA1c was assessed 1.5-6 months post-discharge. The impact of the metformin dose and posttreatment FD on the ΔHbA1c level was analyzed, along with other factors affecting posttreatment FD. Results The analysis included 89 patients (41 on metformin, 21 newly treated; 48 not on metformin, 17 newly treated). Both pre- and posttreatment FD were linked to ΔHbA1c levels in the metformin group. The metformin dose correlated with posttreatment FD but not with pretreatment FD. A significant relationship was observed between ΔHbA1c and the metformin dose. A multiple regression analysis identified posttreatment FD and metformin dose as significant independent factors influencing ΔHbA1c levels. Additionally, diabetic peripheral neuropathy and diabetes duration were found to diminish the effectiveness of metformin, likely due to decreased posttreatment FD. Conclusion FD may independently contribute to the dose-dependent HbA1c-lowering effects of metformin.