Effects of Increasing Metformin Dose vs Adding/Switching to Dipeptidyl Peptidase-4 Inhibitors on Glycemic Control in Patients with Type 2 Diabetes

Introduction Metformin has dose-dependent hypoglycemic effects on patients with type 2 diabetes (T2D). In Japan, metformin has been prescribed at lower doses than in Western countries. We analyzed the effect of increasing the metformin dose on glycemic control and compared it to a combination therapy with dipeptidyl peptidase-4 inhibitors (DPP-4i) and a replacement therapy with DPP-4i. Methods This is a cohort study using a Japanese claims database. Patients with T2D who had been initially treated with low-dose metformin (>= 500 mg/day and < 1000 mg/day) and then given a prescription change by increasing metformin to a higher dose (>= 1000 mg/day) (increased-dose), adding DPP-4i (drug-added), or switching to DPP-4i (drug-switched) were included in this study. The primary outcome was the change in HbA1c levels at 12 months from the baseline period. Results Among 2,726,437 patients with T2D, 494 were included. Of these patients, 226, 240, and 28 patients were classified as increased-dose, drug-added, and drug-switched groups, respectively. The HbA1c levels at 12 months from the index significantly decreased compared to that during the baseline period. The change was the highest in the drug-added group (- 1.06%), followed by the increased-dose (- 0.91%) and the drug-switched groups (- 0.37%). Among the subset of patients who did not receive any antidiabetic drugs other than metformin or DPP-4i, the highest change in HbA1c levels was observed in the increased-dose group (- 0.84%), followed by the drug-added (- 0.67%) and the drug-switched (- 0.42%) groups. The order of decrease from baseline remained the same for all the study groups after the propensity score weighting adjustment. Conclusion The effect on glycemic control when increasing the metformin dose was studied in patients who had been receiving low-dose metformin. Increasing metformin dosage shows effectiveness and could be one of the next treatment options in patients who were prescribed low-dose metformin as the first-line treatment.