A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study

Abstract

Aims To compare the efficacy and safety of adding low‐dose lobeglitazone (0.25 mg/day) or standard‐dose lobeglitazone (0.5 mg/day) to patients with type 2 diabetes mellitus (T2DM) with inadequate glucose control on metformin and dipeptidyl peptidase (DPP4) inhibitor therapy. Materials and Methods In this phase 4, multicentre, double‐blind, randomized controlled, non‐inferiority trial, patients with T2DM insufficiently controlled by metformin and DPP4 inhibitor combination therapy were randomized to receive either low‐dose or standard‐dose lobeglitazone. The primary endpoint was non‐inferiority of low‐dose lobeglitazone in terms of glycaemic control, expressed as the difference in mean glycated haemoglobin levels at week 24 relative to baseline values and compared with standard‐dose lobeglitazone, using 0.5% non‐inferiority margin. Results At week 24, the mean glycated haemoglobin levels were 6.87 ± 0.54% and 6.68 ± 0.46% in low‐dose and standard‐dose lobeglitazone groups, respectively (p = .031). The between‐group difference was 0.18% (95% confidence interval 0.017‐0.345), showing non‐inferiority of the low‐dose lobeglitazone. Mean body weight changes were significantly greater in the standard‐dose group (1.36 ± 2.23 kg) than in the low‐dose group (0.50 ± 1.85 kg) at week 24. The changes in HOMA‐IR, lipid profile and liver enzyme levels showed no significant difference between the groups. Overall treatment‐emergent adverse events (including weight gain, oedema and hypoglycaemia) occurred more frequently in the standard‐dose group. Conclusions Adding low‐dose lobeglitazone to metformin and DPP4 inhibitor combination resulted in a non‐inferior glucose‐lowering outcome and fewer adverse events compared with standard‐dose lobeglitazone. Therefore, low‐dose lobeglitazone might be one option for individualized strategy in patients with T2DM.