Efficacy and safety of fixed-dose dapagliflozin-pioglitazone in Indian adults with type 2 diabetes: a phase 3 PRO-1 trial.

BACKGROUND

To assess the efficacy and safety of a fixed-dose combination (FDC) of dapagliflozin and pioglitazone versus a loose combination (LC) in Patients with Type 2 Diabetes Mellitus inadequately controlled on earlier metformin containing mono therapy. MATERIALS AND

METHODS

This 12-week PRO-1 study was a randomized, open-label, multicenter phase 3 trial that enrolled 180 Indian adults with T2DM, Glycated Hemoglobin (HbA1c) > 7.5% to 10% inadequately controlled with metformin. The participants received once-daily FDC (dapagliflozin 10 mg/pioglitazone 15 mg) or equivalent LC therapy (1:1 randomization). The primary endpoint was the HbA1c change (non-inferiority margin, 0.3). The secondary endpoints included fasting plasma glucose (FPG), postprandial glucose (PPG), and HbA1c < 7.5%.

RESULTS

At week 12, the least-squares mean HbA1c reduction was − 1.20% (FDC) versus − 1.02% (LC). A between-group difference of − 0.18% (95% CI: −0.56 to 0.20) demonstrated non-inferiority. FPG decreased by − 8.6 mg/dL (FDC) and − 12.0 mg/dL (LC); PPG decreased by − 28.2 mg/dL and − 29.5 mg/dL, respectively. Target HbA1c < 7.5% was achieved in 52.9% (FDC) versus 54.8% (LC) of patients. (mITT population; p = 0.877). Both regimens were generally well tolerated; adverse events were more frequent with the fixed-dose combination than with the loose combination (8.9% versus 1.1%, p = 0.034), but were mild and self-limiting, with no serious events, hypoglycemia, or treatment discontinuation in either group.

CONCLUSIONS

The fixed-dose combination of dapagliflozin and pioglitazone was non inferior to separate administration with respect to glycemic efficacy in Indian adults with inadequately controlled type 2 diabetes mellitus receiving metformin, with a favorable and comparable safety profile. TRIAL REGISTRATION: CTRI/2024/09/073221.