Efficacy and safety of pioglitazone versus dapagliflozin as an add-on to metformin and alogliptin combination therapy: the EPIDOTE study

We investigated the efficacy and safety of pioglitazone compared to dapagliflozin when added to metformin plus alogliptin for patients with type 2 diabetes. The patients (n = 133) were randomized to receive pioglitazone (n = 65) or dapagliflozin (n = 68) in addition to metformin and alogliptin therapy for 26 weeks. The primary endpoint was a change in HbA1c. The non-inferiority margin for HbA1c reduction was 0.4%. The adjusted mean change of HbA1c at week 26 was - 0.75% with pioglitazone and - 0.88% with dapagliflozin (mean difference: 0.12% [95% CI - 0.09 to 0.34]). The adjusted mean change of HOMA-IR at week 26 was - 1.55 with pioglitazone and - 1.96 with dapagliflozin (mean difference: 0.41 [95% CI - 0.01 to 0.83]). Lipid profiles were similar between the groups. The proportion of patients achieving HbA1c < 6.5% was similar between groups. Pioglitazone added to metformin and alogliptin significantly improved glycemic control in patients with type 2 diabetes, and was non-inferior to dapagliflozin. This study suggests that pioglitazone could be an effective and safe option for patients with inadequate glycemic control on metformin and DPP4i.