A Multicenter, Randomized, Open-Label Study to Compare the Effects of Gemigliptin Add-on or Escalation of Metformin Dose on Glycemic Control and Safety in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Treated with Metformin and SGLT-2 Inhibitors (SO GOOD Study)

<bold>Background: </bold>We aimed to compare efficacy and safety between gemigliptin add-on and escalation of the metformin dose in patients with inadequately controlled type 2 diabetes mellitus (T2DM) despite treatment with metformin and SGLT2 inhibitors.<bold>Methods: </bold>This study was a multicenter, randomized, open-label, active-controlled, parallel-group comparative study. Patients with T2DM uncontrolled on metformin and SGLT2 inhibitors were randomized to receive gemigliptin 50 mg as an add-on (GEM group, n = 37) or escalation of the metformin dose (500 mg, MET group, n = 38) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to week 24.<bold>Results: </bold>At weeks 12 and 24, the reduction in HbA1c levels was significantly greater in the GEM group than in the MET group (GEM vs. MET = -0.64% +/- 0.34% vs. -0.36% +/- 0.50%, p = 0.009 at week 12; -0.61% +/- 0.35% vs. -0.33% +/- 0.70%, p = 0.045 at week 24). The proportions of patients who achieved target HbA1c levels of <7.0% at weeks 12 and 24 and <6.5% at week 12 were greater in the GEM group than in the MET group. An index of beta-cell function was also significantly improved in the GEM group. The safety profiles were similar between the two groups.<bold>Conclusions: </bold>Gemigliptin add-on therapy may be more effective than metformin dose escalation in patients with T2DM insufficiently controlled using metformin and SGLT2 inhibitors, without safety concerns. This trial is registered with CRIS_number: KCT0003520.