Improvement of Glycemic Control by Metformin Is Associated With Frequency of Defecation Before Treatment in Patients With Type 2 Diabetes Mellitus

Background: It was recently reported that metformin induces glucose excretion in the terminal ileum. This study reassessed the ability of metformin to promote defecation and its relationship with the glycated hemoglobin (HbA(1c)) level in patients with type 2 diabetes mellitus (T2DM).Methods: We retrospectively assessed the frequency of defecation (FD) in patients with T2DM who were admitted to our hospital for glycemic control between April 2017 and March 2022. We examined the FD associated with initiation of metformin or a sodium-glucose cotransporter-2 inhibitor (SGLT2i) by calculating the change in FD after starting treatment (Delta FD). Next, we compared the FD variables (Delta FD, the FD ratio and FD before and after starting treatment) and the change in glycated hemoglobin (Delta HbA(1c)) at 1.5 and 6 months after discharge between the two treatment groups with no change in medications except for minor adjustments in the insulin dose.Results: Fifty-five patients were included (metformin group, n = 30; SGLT2i group, n = 25). The mean FD increased significantly after the maximum dose was reached in the metformin group (from 0.70 +/- 0.19 to 0.83 +/- 0.18 times/day; P = 0.001) but not in the SGLT2i group. Surprisingly, there was no significant relationship between Delta FD or the FD ratio before and after starting treatment and the Delta HbA(1c) in either treatment group. However, there was a significant correlation of FD before and after starting metformin with the Delta HbA(1c) (r =-0.467, P = 0.009 and r =-0.509, P = 0.004, respectively). Multivariate analysis found a significant correlation of FD before and after starting metformin with Delta HbA(1c) (P < 0.05). However, there was no correlation of FD with Delta HbA(1c) before or after starting an SGLT2i.Conclusions: Metformin improves HbA(1c) in patients with T2DM in an FD-associated manner but not in an FD change-associated manner. Given that Delta HbA(1c) was associated with FD both after and before starting metformin, we suggest that the effects of this agent may be influenced by the pretreatment FD as well as conventional dose dependence. However, metformin did increase the FD, but the reason for this phenomenon is currently unknown.